Effect of pacing mode on sleep disturbance

 The relationship between pacing mode and sleep is not yet known, and therefore polysomnography was used to evaluate the effect. A total of 16 patients (8 men and 8 women; mean age, 72 ± 9 years) with DDD pacemakers made up the study population. Of these 16 patients, 8 patients had complete AV block and 8 patients had sick sinus syndrome. The recording was done twice in VVI and DDD modes. Between VVI mode and DDD mode, sleep latency time (VVI mode: 38 ± 25, DDD mode 23 ± 27 min), frequency of temporary waking (8.3 ± 6.7, 3.7 ± 2.9 times), the number of episodes of apnea (59 ± 84, 36 ± 55 times, the apnea–hypopnea index (AHI) (15 ± 18, 10 ± 13), and efficacy of sleep (72% ± 10%, 81% ± 11%) were significantly different. Also, the apnea index improved significantly in DDD mode. There was no significant difference in total sleep time and in total duration of temporary waking between the two groups. From the study results, a reduction in sleep disturbance was achieved when DDD pacing mode was chosen, rather than VVI mode. Furthermore, efficacy of sleep also improved significantly compared with VVI mode. Interestingly, sleep apnea syndrome in four patients with AHI ≧ 15 notably ameliorated when DDD mode was chosen; however, the mechanism involved in amelioration is still ambiguous and needs further assessment. Received: October 4, 2002 / Accepted: February 21, 2003     

Developmental change in the voltage-dependence of the pacemaker current, if, in rat ventricle cells

 Myocytes were isolated from newborn and adult rat ventricle. Using the whole-cell patch clamp, the two cell populations were compared for the presence of the hyperpolarization-activated pacemaker current i_f. As in other mammalian species, the threshold voltage in acutely dissociated adult rat myocytes was extremely negative (–113 ± 5 mV; n=12). In contrast, threshold in newborn cells was relatively positive, regardless of whether measured in acutely dissociated (–72 ± 2 mV; n=6) or cultured cells (–70 ± 2 mV; n=9). Current density was not reduced in the adult. These results suggest that with development the ventricle assumes its non-pacemaker function, at least in part, by a shift of the voltage dependence of i_f outside the physiological range. Received: 8 August 1996 / Received after revision and accepted: 29 October 1996     

Common effects of touch and vision on postural parameters

Subjects stood upright with the index finger of the right hand either touching a nearby surface gently or not touching it at all and with the eyes either open or closed. Trajectories of the center of pressure (COP) were analyzed as fractional Brownian motion. The extracted parameters were the effective diffusion (D) coefficients and Hurst (H) exponents for short-term time intervals (corresponding to positively correlated random walks) and long-term time intervals (corresponding to negatively correlated random walks). Gentle tactile contact reduced the effective stochastic activity measured by D to the same extent as the availability of vision. Further, touch interacted with time interval in the same way as vision, with the correlated activity closer to H = 0.5 at both time scales when the finger contacted the nearby surface. The results corroborate and extend major features of recent investigations of haptic influences on posture and recent analyses of vision’s influence on the fractional Brownian motions of the COP. Discussion focused on (a) the equivalence of expropriospecific information (about the body’s orientation to the environment) registered haptically and visually and (b) the possibility that postural sway may reflect exploratory motions in the short term (obtaining information about the postural system) and performatory motions in the long term (using this information). Received: 17 February 1997 / Accepted: 18 June 1997     

The effects of interfering with GTP-binding proteins on the activation mechanism of calcium release-activated calcium current

 In electrically non-excitable cells, Ca²⁺ entry is mediated predominantly by the store-operated Ca²⁺ influx pathway, which is activated by emptying the intracellular Ca²⁺ stores. Just how the Ca²⁺ content of the stores is communicated to the activity of store-operated Ca²⁺ channels in the plasma membrane is unclear. It has been suggested that, in some cell types, the link is accomplished by either a small or a heterotrimeric GTP-binding protein, which is inhibited by guanosine 5′-O-(3-thiotriphosphate) (GTP[γ-S]) and, in some cases, pertussis toxin. Using the whole-cell patch-clamp technique to directly measure the store-operated Ca²⁺ current I _CRAC (Ca²⁺-release-activated Ca²⁺ current) in RBL cells, we report that manipulations designed to interfere with GTP-binding protein activity (dialysis with GTP[γ-S], exposure to pertussis toxin) routinely fail to affect the activation of I _CRAC. However, these agents alter the activity of a K⁺ current in the same cells, demonstrating biological activity. Furthermore, activation of I _CRAC does not seem to require the presence of a pre-existing diffusible messenger in the cytoplasm to any appreciable extent because the current reaches the same amplitude irrespective of the whole-cell dialysis time. We conclude that neither a mobile pre-existing molecule nor a GTP-dependent step is necessary for the activation of I _CRAC in RBL-1 cells. Received: 9 September 1998 / Received after revision and accepted: 2 November 1998     

Strophanthidin-induced gain of Ca2+ occurs during diastole and not systole in guinea-pig ventricular myocytes

 We have investigated the effects of inhibiting the Na-K pump with strophanthidin on the intracellular Ca²⁺ concentration ([Ca²⁺]_i), sarcoplasmic reticulum (s.r.) Ca²⁺ content and membrane currents. s.r. Ca²⁺ content was measured by integrating the Na-Ca exchange current resulting from application of 10 mM caffeine. The application of strophanthidin increased both diastolic and systolic [Ca²⁺]_i. This was accompanied by an increase of s.r. Ca²⁺ content from a resting value of 17.9±1.5 μmol/l to 36.9±3.3 μmol/l (n=16) after 5 min. Systolic fluxes of Ca²⁺ into and out of the cell before and during strophanthidin application were also measured. Ca²⁺ efflux (measured as the integral of the Na-Ca exchange tail current) rose steadily in the presence of strophanthidin, while Ca²⁺ influx (the integral of the L-type Ca²⁺ current) was reduced. In spite of this, s.r. Ca²⁺ content rose substantially. In the presence of Cd²⁺ (100 μM), which inhibits the L-type Ca²⁺ current, strophanthidin had negligible effects on current suggesting that Ca²⁺ influx via Na-Ca exchange during depolarization does not account for the increase of s.r. Ca²⁺ content. This suggests that changes of Ca²⁺ flux during systole are not responsible for the strophanthidin-induced increase of s.r. Ca²⁺. We conclude that the primary mechanism by which the cardiac cell gains Ca²⁺ when the Na-K pump is inhibited is by a net influx during diastole. Received: 2 November 1998 / Received after revision: 8 December 1998 / Accepted: 9 December 1998     

Influence of object position and size on human prehension movements

 Prehension movements of the right hand were recorded in normal subjects using a computerized motion analyzer. The kinematics and the spatial paths of markers placed at the wrist and at the tips of the index finger and thumb were measured. Cylindrical objects of different diameters (3, 6, 9 cm) were used as targets. They were placed at six different positions in the workspace along a circle centered on subject’s head axis. The positions were spaced by 10° starting from 10° on the left of the sagittal axis, up to 40° on the right. Both the transport and the grasp components of prehension were influenced by the distance between the resting hand position and the object position. Movement time, time to peak velocity of the wrist and time to maximum grip aperture varied as a function of distance from the object, irrespective of its size. The variability of the spatial paths of wrist and fingers sharply decreased during the phase of the movement prior to contact with the object. This indicates that the final position of the thumb and the index finger is a controlled parameter of visuomotor transformation during prehension. The orientation of the opposition axis (defined as the line connecting the tips of the thumb and the index finger at the end of the movement) was measured. Several different frames of reference were used. When an object-centered frame was used, the orientation of the opposition axis was found to change by about 10° from one object position to the next. By contrast, when a body-centered frame was used (with the head or the forearm as a reference), this orientation was found to remain relatively invariant for different object positions and sizes. The degree of wrist flexion was little affected by the position of the object. This result, together with the invariant orientation of the opposition axis, shows that prehension movements aimed at cylindrical objects are organized so as to minimize changes in posture of the lower arm. Received: 2 July 1996 / Accepted: 5 October 1996     

Analysis of the time course of calcium-activated chloride “tail” currents in rabbit portal vein smooth muscle cells

 The time course of calcium-activated chloride ”tail” currents (I _tail) in single cells of the rabbit portal vein was studied. These currents were activated by the influx of calcium through voltage-dependent calcium channels (VDCCs). At –50 mV, I _tail decayed exponentially with a time constant (τ) of 80–100 ms that was independent of amplitude and was similar to the τof the decay of spontaneous transient inward currents (STICs; calcium-activated chloride currents). The decays of the STIC and I _tail had a similar voltage dependence between –50 and –110 mV and were similarly affected by the chloride channel blocker, niflumic acid. However, at more positive potentials (–20 to +40 mV), I _tail was sustained for the duration of the test pulse in most cells, in contrast to STICs which decayed exponentially. At very positive potentials (e.g. +100 mV), when little calcium enters the cell through VDCCs, I _tail decayed exponentially. Measurement of calcium current (I _Ca) at various potentials showed that the VDCCs did not inactivate fully at potentials between –20 and +30 mV. We propose that at negative potentials the decay of I _tail is determined by slow gating of the chloride channel, but at positive potentials a sustained I _tail is produced by persistent influx of calcium through non-inactivating VDCCs. Received: 19 March 1996 / Received after revision: 22 May 1996 / Accepted: 23 May 1996     

Evidence for a rapid,direct effect on epithelial monolayer integrity and transepithelial transport in response to Salmonella invasion

 In cultured monolayers of high-resistance Madin-Darby Canine Kidney (MDCK) cells, infection with Salmonella typhimurium SL1344 resulted in a dose- and time-dependent increase in transepithelial conductance (G _t) and short-circuit current (I _sc). There was a direct linear relationship between the S. typhimurium-induced increments in I _sc and G _t suggesting that this early change in epithelial parameters is, in part, the result of a cellular conductance change most probably at the apical membrane. An additional wild-type S. typhimurium strain, SR11, and an invasion-deficient isogenic mutant SB111 carrying a non-polar mutation in invA were used to confirm that the S. typhimurium-induced change in epithelial electrical parameters is directly linked to the invasion process. The S. typhimurium-induced change in epithelial electrical parameters was markedly attenuated in Na⁺-free choline medium. Addition of piretanide (10^–4 M, basal side) failed to affect the increased epithelial conductance and I _sc after a 40-min incubation with S. typhimurium. NPPB (5×10^–4 M) added to the apical medium reduced the S. typhimurium-stimulated I _sc by 28%, but G _t was not significantly reduced. It is unlikely that the S. typhimurium-induced I _sc is due to Cl^–secretion. Staining of S. typhimurium-infected MDCK I monolayers with TRITC-phalloidin revealed marked alterations of F-actin; diffuse intracellular accumulations of F-actin corresponding to the presence of invading bacteria were observed by 15 min. After 60 min, prominent extrusions of the apical membrane corresponding to previously described ”membrane ruffles” were noted. Marked accumulations of perijunctional F-actin in infected cells corresponded to contraction of the perijunctional actin ring at the apical pole. In adjacent cells marked distortion and stretch of the apical surface was evident. The invasion-deficient invA mutant SB111 failed to induce these morphological changes. These data demonstrate that S. typhimurium invasion induces increased transcellular conductance which does not result from stimulation of Cl^–secretion but instead appears to be predominantly due to increased Na⁺ permeability. The increased membrane conductance is coincident with increased transepithelial inulin permeability indicating that the increment in G _t has an additional ”paracellular” component. The S. typhimurium-induced alterations in epithelial parameters may be related to ”membrane ruffling” and/or to the accompanying changes in cell shape. Received: 17 October 1995 / Received after revision and accepted: 23 February 1996     

Volume-sensitive chloride current activated by hyposmotic swelling in antral gastric myocytes of the guinea-pig

 The characteristics of volume-sensitive chloride current (I _Cl) induced by osmotic cell swelling were studied using the whole-cell patch-clamp technique and cell diameters of antral circular guinea-pig myocytes were simultaneously measured under isosmotic and hyposmotic conditions by using a video image analysis system. At –60 mV, osmotic cell swelling (200 mosmol/l) activated a sustained inward current. Instantaneous current/voltage (I-V) relations obtained by step voltage pulses showed an outward rectification. At potentials above +40 mV, the current exhibited time-dependent decay. The outward current amplitude was decreased and the reversal potential was shifted to more positive potentials by replacement of external Cl^– with gluconate^–, while the current amplitude and the I/V relation were not affected by replacing extracellular Na⁺ with N-methyl-D-glucamine. The anion permeability sequence of the swelling-induced current was I^– (1.80) > Br^– (1.31) > Cl^– (1) > F^– (0.85) > gluconate^– (0.18). The I _Cl was effectively inhibited by the Cl^– channel blockers, 4,4′-diisothiocyanatostilbene-2,2’-disulphonic acid (DIDS, 100 μM), and niflumic acid (10 μM). DIDS suppressed outward current more effectively than inward current. Also, the I _Cl was dose-dependently inhibited by arachidonic acid, an unsaturated fatty acid and also inhibited by other unsaturated fatty acids (linoleic acid and oleic acid) but not by stearic acid, a saturated fatty acid. The inhibitory effect of arachidonic acid on I _Cl was not prevented by indomethacin, a cyclo-oxygenase inhibitor and chelerythrine, a protein kinase C inhibitor. Under whole-cell patch-clamp conditions, the cell diameter was continuously measured using video image analysis, which reflects the change in cell volume. A hyposmotic-stimulation-induced increase of cell diameter was followed by I _Cl activation. In intact single gastric myocytes, relatively severe hyposmotic (176 mosmol/l) superfusing solution increased the cell diameter and the pretreatment with DIDS or with niflumic acid significantly potentiated the above effect of hyposmotic superfusion. These results suggest that volume-sensitive outwardly rectifying chloride current (I _Cl) is present in guinea-pig gastric myocyte and the I _Cl may play a role in smooth muscle cell volume regulation. Received: 6 June 1997 / Received after revision and accepted: 24 July 1997     

Measurement of concentration-response relationships by concentration-ramp application of agonists

Dose-response relationships of agonist- induced membrane currents were obtained during accumulation of agonist and a simultaneously applied dye in the culture dish. The concentration of the dye was continuously measured using a laboratory-made photometer. When the superfusate was switched from the control solution to a test solution containing an agonist and an inert dye (e.g. Fast Green) both accumulated in the bath together and the change of dye concentration altered the intensity of light falling through the objective. The change in light intensity in an area directly surrounding the cell under study was measured by the photometer. The normal microscope lamp was used as the light source and a colour filter was placed between the microscope lamp and the condenser in order to enhance the signal-to-noise ratio of the photometer output. Assuming that the rates of accumulation and clearance of dye are similar to those of the agonist, it is possible to continuously measure the membrane current at given dye and agonist concentrations. To calculate the dose-response curves we calibrated the relationship between the dye concentration and the photometer voltage output. Received: 15 January 1999 / Received after revision: 18 February 1999 / Accepted: 19 March 1999     

Novel transient outward K+ current of mature murine hippocampal neurones

 Hippocampal neurones were freshly isolated from the brain of adult mice and voltage-dependent K⁺ currents were recorded with the whole-cell patch-clamp technique. Three components of transient K⁺ current (IA) were isolated when analyzing data with exponential functions or treating neurones with a variety of voltage protocols and pharmacologic agents. Subtraction of the delayed rectifier current (I _K) from the K⁺ currents elicited after prepulses to –120 mV of varying duration revealed fast (IAf) and slow (IAs) components with decay time constants of 45 ± 8 and 612 ± 140 ms, respectively; the corresponding time constants for the removal of inactivation were 12.3 and 189.6 ms. Both tetraethylammonium and dendrotoxin selectively inhibited IAs. 4-Aminopyridine (4-AP) specifically blocked IAf and 40% of IAs with different affinities. Therefore, the properties of a 4-AP-resistant (IAsR) and a 4-AP-sensitive (IAsS) component of IAs were compared. These data suggest that three distinct subtypes of K⁺ currents contribute to the IA of mature murine hippocampal neurones. Received: 10 April 1996 / Accepted: 11 February 1997     

An endogenous inactivating inward-rectifying potassium current in oocytes of Xenopus laevis

 An endogenous inward-rectifying K⁺ current is described, which is present in native oocytes of some Xenopus laevis donors. Experiments were performed using defolliculated oocytes from donor frogs obtained from two different suppliers. In all oocytes from animals from one source, an inward-rectifying K⁺ current could be elicited with negative pulses from a holding potential of –20 mV in external solutions with a high K⁺ concentration. Increasing external K⁺ concentrations increased the amplitude of this current and shifted the reversal potential towards more positive potentials. In 118 mM KCl, the inward-rectifying K⁺ current partially inactivated between –20 and –80 mV and completely inactivated at more negative membrane potentials; 50% steady-state inactivation occurred near –50 mV. The time course of inactivation of the inward-rectifying current could be well fitted with two exponentials. The slow time constant had values of about 500 ms and was voltage independent. In contrast, the fast time constant and the time to reach the peak inward current decreased with more negative membrane potentials. Ba²⁺, Cs⁺, quinine (all 5 mM) and 50 mM tetraethylammonium partially blocked the inward-rectifying K⁺ current, whereas 10 mM 4-aminopyridine was without blocking effect. The oxidant chloramine-T blocked the inward-rectifying K⁺ current without slowing its inactivation. Received: 21 November 1995 / Received after revison and accepted: 24 May 1996     

An examination of the role of intracellular ATP in the activation of store-operated Ca2+ influx and Ca2+-dependent capacitance increases in rat basophilic leukaemia cells

 The role of ATP in both the activation of store-operated Ca²⁺ current I _CRAC and in Ca²⁺-dependent vesicular fusion was examined in a study of rat basophilic leukaemia (RBL) cells using the whole-cell patch-clamp technique. Fusion was monitored via changes in plasma membrane capacitance. Following a decrease in the levels of intracellular ATP, achieved using the mitochondrial poison antimycin and the ATP synthase inhibitor oligomycin, as well as a reduction of glycolysis by removal of external glucose, I _CRAC activated in a manner similar to control cells when stores are depleted by dialysis with a pipette solution containing either inositol 1,4,5-trisphosphate (InsP ₃) or ionomycin together with a high concentration of EGTA. Dialysis of cells for 150 s with the non-hydrolysable ATP analogue 5′-adenylylimidodiphosphate (AMP-PNP) (2 mM) in addition to the mitochondrial inhibitors also failed to prevent activation of I _CRAC following external application of ionomycin and thapsigargin, when compared with control recordings obtained with 2 mM ATP instead. Ca²⁺-dependent vesicular fusion was triggered by dialysing cells with 10 μM Ca²⁺ and guanosine-5′-O-(3-thiotriphosphate (GTP[γ-S]). The capacitance increase was unaffected by inhibition of glycolysis, mitochondrial inhibitors or dialysis with either AMP-PNP or adenosine 5′-O-(3-thiotriphosphate) (ATP[γ-S]) instead of ATP. We conclude that ATP hydrolysis does not seem to be necessary for the activation of I _CRAC or for the capacitance increases elicited by high concentrations of intracellular Ca²⁺. Received: 1 May 1998 / Received after revision: 16 July 1998 / Accepted: 16 July 1998     

Development of an electrostatic generator for a cardiac pacemaker that harnesses the ventricular wall motion

 A variable-capacitance-type electrostatic (VCES) generator that harnesses ventricular motion was developed with the aim of driving a cardiac pacemaker permanently without a battery. The developed model of the VCES generator was handmade, but it was too large to implant into the thoracic cavity of a laboratory animal. For this reason, to demonstrate its feasibility, a somewhat complicated method that measured the left ventricular wall motion by means of the accelerometer module put on the free wall and reproduced the motion in real time with a vibration mode simulator was used. The VCES generator was vibrated on the simulator, and its generated power was supplied to the cardiac pacemaker, which then stimulated the heart. A mean power of approximately 36 μW was generated, which was enough to drive the cardiac pacemaker. Continuous electric generation and cardiac pacing were performed successfully for more than 2 h in the animal experiment. Received: May 17, 2002 / Accepted: September 10, 2002 Correspondence to:R. Tashiro     

Influence of substrate structure on substrate binding to the renal organic cation/H+ exchanger

 The carrier-mediated exchange of H⁺ for organic cations (”OC/H⁺ exchange”) is the active step in OC secretion in renal proximal tubules. Although hydrophobicity is known to be an important criterion for binding of substrates to this transporter, the degree to which steric parameters of substrate structure influence binding to the exchanger is unclear. We examined this issue by measuring the inhibition of OC/H⁺ exchange produced by a group of quaternary ammonium compounds which share a common structural motif: an N ¹-pyridinium residue. Activity of the OC/H⁺ exchanger was determined by measuring transport of [¹⁴C]tetraethylammonium (TEA) in brush-border membrane vesicles (BBMV) from rabbit renal cortex. Transport was measured in the presence of a pH gradient (pH_in 6.0; pH_out 7.5) to maximize TEA/H⁺ exchange. Apparent inhibitory constants (K _i values) for each test agent were measured. The test agents included 4-phenylpyridiniums and 3-phenylpyridiniums, quinoliniums and acridiniums. The planar structure of these compounds permits a direct test of whether the presence of planar hydrophobic mass in different orientations relative to the pyridinium motif exerts a systematic effect on substrate binding to the OC/H⁺ exchanger. The hydrophobicity of each group of compounds was systematically varied by addition of different substituents at the quaternary nitrogen. Whereas decreases in K _i proved to be proportional to hydrophobicity, the position of the phenyl-ring substituent(s) had no effect on substrate interaction with the exchanger. The results led to the development of a preliminary quantitative structure–activity relationship (QSAR) correlating substrate hydrophobicity and substrate binding to the OC/H⁺ exchanger. This QSAR was used to predict the binding of 1-methyl-4-phenylpyridinium (MPP⁺), (+) and (–)nicotine, (+) and (–)ephedrine, quinine and quinidine to the OC/H⁺ exchanger. Molecular graphics representation of the 3D structures of the test agents was used to develop a working model of a hydrophobic, planar receptor surface on the OC/H⁺ exchanger against which substrates are suggested to interact during binding. Development of the QSAR and receptor surface model open the way to quantitative tests of the specific physical and structural determinants of substrate selectivity by the renal OC/H⁺ exchanger. Received: 20 July 1998 / Received after revision and accepted: 19 October 1998     

Electrophysiological actions of quinine on voltage-dependent currents in dissociated rat taste cells

 How taste receptor cells participate in encoding disparate compounds into distinct taste qualities represents a fundamental problem in the study of gustatory transduction mechanisms. Quinine is the most common stimulus employed to represent bitterness yet its electrophysiological consequences on voltage-dependent ion channels in the taste receptor cell have not been elucidated in detail. This study examines such effects on taste receptor cells dissociated from the foliate and circumvallate papillae of the rat. Outward potassium currents, which include transient, sustained and calcium-activated components, were reversibly inhibited by bath application of quinine, with an IC₅₀ of 5.1×10^–6 M. The time course of the current traces, along with voltage shifts in normalized conductance and inactivation curves, suggests that multiple mechanisms of inhibition may be occurring. Inwardly rectifying potassium currents were unaffected. Sodium currents, to somewhat higher concentrations of quinine (IC₅₀ = 6.4×10^–5 M), were also reduced in magnitude without noticeable effects on activation or reversal potential but with a shift in inactivation. Calcium currents, visualized with barium as a charge carrier, were enhanced in magnitude by the presence of low concentrations of quinine (10^–5 M) but were suppressed by higher concentrations (10^–4 M). Quinine broadened the waveform of the gustatory action potential and increased the input resistance. These data serve as genesis to future investigations of the signal transduction mechanism of quinine on voltage-dependent currents. Received: 18 November 1996 / Received after revision: 25 February 1997 / Accepted: 5 March 1997     

Influence of pre-target cortical potentials on saccadic reaction times

 Saccades elicited by suddenly appearing targets show a broad distribution of reaction times. This may depend on variations in the subject’s state of preparation before target onset. To test this hypothesis, we recorded scalp event-related potentials from eight human subjects to investigate whether differences in saccadic reaction times (SRTs) are related to differences in cortical slow potentials prior to target onset. Compared with trials with medium SRTs (180–230 ms), trials with fast SRTs (130–180 ms) were found to be preceded by a more negative slow potential and trials with slow SRTs (230–280 ms) were found to be preceded by a more positive slow potential. These results support the hypothesis that cortical activation prior to target appearance influences SRTs. Received: 21 June 1996 / Accepted: 15 January 1997     

Inhibitory effect of phorbol 12, 13 dibutyrate on carbachol-activated nonselective cationic current in guinea-pig gastric myocytes

 The effect of protein kinase C (PKC) on carbachol (CCh)-activated nonselective cationic current (I _CCh) was investigated in guinea-pig gastric myocytes using a PKC activator, phorbol 12, 13 dibutyrate (PDBu). Pretreatment with 1 μ M PDBu suppressed I _CCh by 96.5 ± 2.9% (n = 14) in a reversible manner in nystatin-perforated mode. In the presence of 1 μM chelerythrine , a PKC inhibitor, inhibition of I _CChby PDBu was not seen. In whole-cell mode, the inhibition of I _CCh by PDBu was dependent on intracellular MgATP. In the presence of MgATP in the pipette, PDBu decreased I _CCh by 98.8 ± 1.2% (n = 5) as was observed in nystatin-perforated mode. However, PDBu had little effect on I _CCh in the absence of MgATP in the pipette; the extent of inhibition was 12.7 ± 4.3% (n = 8). PDBu also suppressed the generation of cationic current induced by intracellularly perfused GTP[γS]. In the PDBu-pretreated group (n = 9) and PDBu-untreated control group (n = 6), GTP[γS]-induced currents were 6.7 ± 2.4 pA and 236 ± 23 pA, respectively. These results suggest that PKC modulates I _CCh at postreceptor sites via protein phosphorylation. Received: 4 April 1997 / Received after revision: 27 June 1997 / Accepted: 3 June 1997     

The oculomanual coordination control center takes into account the mechanical properties of the arm

 When the eyes and arm are involved in a tracking task, the characteristics of each system differ from those observed when they act alone: smooth pursuit (SP) latency decreases from 130 ms in external target tracking tasks to 0 ms in self-moved target tracking tasks. Two models have been proposed to explain this coordination. The common command model suggests that the same command be addressed to the two sensorimotor systems, which are otherwise organized in parallel, while the coordination control model proposes that coordination is due to a mutual exchange of information between the motor systems. In both cases, the interaction should take into account the dynamic differences between the two systems. However, the nature of the adaptation depends on the model. During self-moved target tracking a perturbation was applied to the arm through the use of an electromagnetic brake. A randomized perturbation of the arm increased the arm motor reaction time without affecting SP. In contrast, a constant perturbation produced an adaptation of the coordination control characterized by a decrease in arm latency and an increase in SP latency relative to motor command. This brought the arm-to-SP latency back to 0 ms. These results support the coordination control model. Received: 24 November 1997 / Accepted: 1 July 1998