The exercise pressor response to sustained handgrip does not augment blood flow in the contracting forearm skeletal muscle

Previous studies have advanced the concept that during sustained handgrip (SHG) reflex increases in blood pressure are able to partially offset increases in tissue pressure and thus effectively maintain increases in muscle blood flow during mild to moderate levels of sustained handgrip. However, this concept is based upon measurements of blood flow to the entire forearm. The aim of this study was to evaluate this concept by simultaneously measuring time-dependent changes in systemic arterial pressure and blood flow in an active muscle during the actual period of exercise. To accomplish this aim, we measured ¹³³Xenon washout from the extensor carpi radialis longus muscle over 3 min of SHG at 15, 30 and 45% of maximal voluntary contraction (MVC). During sustained handgrip at 15% MVC, muscle blood flow increased more than 20 fold from rest to exercise (P < 0.05), even though mean arterial pressure increased by only 12 ± 4 mmHg. This large exercise-induced hyperaemia was abolished during SHG at both 30 and 45% MVC, despite large and progressive increases in mean arterial pressure of 29 ± 3 and 54 ± 5 mmHg, respectively. We conclude that at levels of handgrip above 15% MVC blood pressure ceases to be an important determinant of blood flow in the active skeletal muscle. Importantly, the increases in forearm blood flow that have been reported previously with such levels of static handgrip do not appear to be directed to the most active muscle.     

Subcutaneous and skeletal muscle vascular responses in human limbs to lower body negative pressure

Jacobsen , T. N., Nielsen , H. V., Kassis , E. & Amtorp o S. 1992. Subcutaneous and skeletal muscle vascular responses in human limbs to lower body negative pressure. Acta Physiol Scand 144 , 247–252. Received 8 March 1991, accepted 7 Novcmber 1991. ISSN 0001–6772. Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark Cardiopulmonary baroreceptor unloading in humans comparably increases sympathetic discharge to skeletal muscle in the forearm and calf, but blood flow studies have disclosed differential rather than uniform vasomotor responses in the extremities. The aim of the present study was to address the issue of differential effects of orthostatic stress on forearm and calf vascular adjustment and to extend previous studies by determining changes in vascular responses separately in various vascular beds of the limbs. The local [¹³³Xenon] washout method was used for recording blood flow rates in subcutaneous tissue and skeletal muscle. Simultaneous recordings from the forearm and calf were performed in 11 healthy young males during lower body negative pressure at —10 mmHg. Heart rate, arterial mean and pulse pressures did not change during lower body negative pressure. In the forearm blood flow rates decreased significantly, in subcutaneous tissue by 16 ± 2% (mean ± SEM) and in skeletal muscle by 16 ± l%. In the calf lower body negative pressure induced a significant decrease in blood flow rates of 17 ± 3% in subcutaneous tissue and of 30 ± 2% in skeletal muscle. This vasoconstriction in calf skeletal muscle was consistently disclosed in both legs and was about the same magnitude in each calf when studied with the one leg exposed to lower body negative pressure and the other outside the lower body negative pressure chamber. These findings suggest that during unloading of cardiopulmonary afferents, reflex sympathetic activation as an important autonomic adjustment to orthostatic stress is accompanied by uniform vasoconstriction in subcutaneous and skeletal muscle vascular beds of human limbs.     

Skeletal muscle excitation-contraction coupling I

Porcine skeletal muscle fibers were studied to determine if the defect in malignant hyperthermia involves transverse tubule (TT) to sarcoplasmic reticulum (SR) communication. Pelled (mechanically skinned) skeletal muscle fibers from normal and malignant hyperthermia susceptible (MHS) pigs were stimulated with Cl^– to ionically depolarize transverse tubules and thereby trigger Ca²⁺ release from SR. Caffeine was used to directly stimulate the Ca²⁺-induced Ca²⁺ release mechanism (CaIR) of the sarcoplasmic reticulum. Calcium released from internal fiber stores was monitored as Ca²⁺-activated isomeric force generation in the form of tension transients. Cl^–-induced tension transients result from a primary component of Ca²⁺ release which triggers a secondary CaIR component; CaIR and caffeine contractures were eliminated by procaine. The primary component of Cl^–-induced SR Ca²⁺ release was indistinguishable for MHS and normal skeletal peeled fibers at all TT resting and Cl^– stimulation conditions. Only the magnitude of the secondary CaIR component was significantly larger in MHS fibers. The [Ca²⁺] threshold for secondary CaIR was lowered by resting TT depolarization in both normal and MHS fibers. Conditions for resting TT hyperpolarization selectively reduced the magnitude of the secondary CaIR component of MHS fibers, making them indistinguishable from normal.     

Interactive effects between isometric exercise and mental stress on the vascular responses in glabrous and nonglabrous skin

Cutaneous vascular responses to mental arithmetic (MA) and handgrip exercise (HG) were studied independently and combined at different local skin temperatures (T _loc). MA and HG induced (P < 0.05) vasoconstrictor responses in glabrous and nonglabrous skin at a higher level of T _loc, resulting in a nonadditive effect of these two stresses.     

Leg muscle blood flow during reactive hyperemia

Summary In normal man at rest transition from the supine to the upright body position is accompanied by autoregulation of the blood flow to tissues in the dependent extremities.In 11 young healthy males the influence of postural changes and external pressure changes on the blood flow in the anterior tibial muscle during reactive hyperemia was studied. The muscle blood flow was evaluated by means of the Xenon-133 wash-out technique. Transmural pressure changes in the resistance vessels were estimated by measuring the systolic blood pressure at ankle level, using the strain-gauge plethysmograph technique. The mean leg muscle blood flow increased from 48 ml·100 g^–1·min^–1 in a body position with the legs elevated 65 cm above heart level, to 101 ml·100 g^–1·min^–1 in the supine position, and to 151 ml·100 g^–1·min^–1 in a sitting position with dependent legs 70 cm below heart level. The muscle blood flows increased from 92 ml·100 g^–1·min^–1 at ambient pressure to 139 ml·100 g^–1·min^–1 at a subatmospheric pressure of –50 mm Hg. The differences were highly significant (P<0.001). Systemic blood pressure measured at heart level did not change during postural changes and external pressure changes. The post-ischemic muscle blood flow was found to increase with the increasing vascular transmural pressure.It is concluded that during reactive hyperemia the normal compensatory vaso-reactions can be inactivated, so that the vessels react passively to changes in transmural pressure.     

The effect of polycythemia on blood flow in working and non-working skeletal muscle

The effect of acutely induced polycythemia on blood flow and viscosity in the vasodilated vascular bed of working and non-working skeletal muscle was studied. In 12 mongrel dogs anesthetized with thiopental sodium the calf muscle of one hind limb was isolated. Vasodilation was induced either by sciatic stimulation setting the muscle at maximal work or by i.a. infusion of papaverine. Blood flow was measured at different perfusion pressures before and after infusion of 300 ml packed homologous red cells. Blood viscosity in vitro was determined in a coneplate viscometer. Apparent viscosity in vivo was analyzed by comparing pressure-flow relationships for blood and a reference solution. Polycythemia decreased blood flow by 35% in the non-working muscle but less than 10% in the working muscle at comparable perfusion pressures. Blood viscosity in vitro increased by 35% at low shear rates. Apparent viscosity in vivo increased by 35% in the non-working muscle but less than 10% in the working muscle. The flow impairment induced by polycythemia was far more pronounced in the non-working skeletal muscle indicating a flow facilitation by the rhythmic muscle contractions. Erythrocyte flow in fact increased in the working muscle after induced polycythemia while decreased in the non-working muscle.     

Determination of the local muscular blood flow in the hind limbs of dogs during electrolysis of electrically conducting vascular prostheses preimplanted into the abdominal aorta

The peripheral blood flow in the hind limbs was studied in experiments on 25 mongrel dogs during electrolysis of electrically conducting vascular prostheses preimplanted into the abdominal aorta. After restoration of the trunk blood flow, a positive electrical potential of 3–4 V was applied to the prosthesis by means of a current conductor. The tissue blood flow was determined by a radiographic method using xenon-133. The results showed that during application of the positive potential to the electrically conducting prosthesis the tissue blood flow in the hind limbs of the dogs increased, but after application of the current stopped it fell to its initial level. It is concluded that to obtain a prolonged and stable increase in the tissue blood flow in the limbs of animals, a positive potential from a dc source must be applied continuously to the electrically conducting prosthesis.All-Union Research Institute of Clinical and Experimental Surgery, Ministry of Health of the USSR. Department of Clinical Surgery, I. M. Sechenov First Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR A. M. Chernukh.) Translated from Byulleten Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 2, pp. 148–149, February, 1978.     

Activation and inhibition of muscle and cutaneous postganglionic neurones to hindlimb during hypothalamically induced vasoconstriction and atropine-sensitive vasodilation

Summary Subcutaneous adipose tissue blood flow (ATBF) was examined in 8 subjects during 6 h exercise on a bicycle ergometer. The initial work load was 118 W corresponding to about 50% of maximal work capacity. The oxygen uptake increased from 0.26 l ·min^–1 at rest to about 1.6l·min^–1 during work. In 7 subjects ATBF increased, in 1 it remained constant. After 3 h exercise ATBF at an average reached values 3–4 times the control value. This increase was maintained for the remaining work periods. The increase was significant at the 5% level. Plasma free fatty acids increased 7-, plasma glycerol 10-fold during work.     

Functional significance of collateral blood flow in working skeletal muscle of the dog

Summary The semitendinosus muscle of the dog is supplied by two separate arteries and drained by two corresponding veins. In the muscles used in this study no blood entering via the distal artery was found to leave via the proximal vein during perfusion through both arteries (orthograde perfusion). Therefore, collateral flow (CF) could be determined as proximal venous outflow during occlusion of the proximal artery. During orthograde perfusion total blood flow averaged 12 ml × min⁻¹ × 100 g⁻¹ at rest and 58.4 ml × min⁻¹ × 100 g⁻¹ during exercise. CF was found to average 6.2 ml × min⁻¹ × 100 g⁻¹ at rest and increased to 9.2 ml × min⁻¹ × 100 g⁻¹ during exercise. CF was sufficient to cover the metabolic demand of resting muscle. During exercise the O₂-uptake ( ) of the distal muscle portion was increased 13.4 fold in comparison to a 3.1 fold increase in the proximal muscle portion. The average contractile power decreased by 46%. Additional infusion of adenosine into the distal artery resulted in an increase of CF to 11.4 ml × min⁻¹ × 100 g⁻¹ and of orthograde flow to 71 ml × min⁻¹ × 100 g⁻¹. The average contractile power of the muscle increased by 13%. Both orthograde flow and CF were found to decrease with increasing muscle load. But this decrease was significantly more pronounced in the case of CF especially at a. lower range of loads. It is concluded that after acute occlusion of orthograde flow, CF is limited by the number, the size and the dilatory capacity of precapillary network vessels. Furthermore, CF is influenced considerably by changes of extravascular support. Presented in part at the 43rd Meeting of the Deutsche Physiologische Gesellschaft [9] and at the XXVI International Congress of Physiological Sciences, New Delhi [6] Supported by the Deutsche Forschungsgemeinschaft (Hi 137/6)     

Changes in intracellular ion activities induced by adrenaline in human and rat skeletal muscle

To study the stimulating effect of adrenaline (ADR) on active Na⁺/K⁺ transport we used double-barrelled ion-sensitive micro-electrodes to measure the activities of extracellular K⁺ (aK_e) and intracellular Na⁺ (aNa_i) in isolated preparations of rat soleus muscle, normal human intercostal muscle and one case of hyperkalemic periodic paralysis (h.p.p.). In these preparations bath-application of ADR (10⁻⁶ M) resulted in a membrane hyperpolarization and transient decreasesaK_e andaNa_i which could be blocked by ouabain (3×10⁻⁴ M). In the h.p.p. muslce a continuous rise ofaNa_i induced by elevation ofaK_e to 5.2 mM could be stopped by ADR. In addition, the intracellular K⁺ activity (aK_i), the free intracellular Ca²⁺ concentration (pCa_i) and intracellular pH (pH_i) were monitored in rat soleus muscle. During ADRaK_i increased, pH_i remained constant and intracellular Ca²⁺ apparently decreased. In conclusion, our data show that ADR primarily stimulates the Na⁺/K⁺ pump in mammalian skeletal muscle. This stimulating action is not impaired in the h.p.p. muscle. Parts of the results have been presented to the German Physiological Society (Ballanyi and Grafe 1987)     

Skeletal muscle perfusion in electrically induced dynamic exercise in humans

Leg blood flow, blood pressure and metabolic responses were evaluated in six men during incremental one-legged dynamic knee extension exercise tests (no load exercise - 40 W); one performed with voluntary contractions (VOL) and one with electrically induced contractions (EMS). Pulmonary oxygen uptake was the same in both exercise modes, but the ventilatory coefficient was 2–5 L per L O₂ higher in EMS than VOL (P < 0.05). Heart rate and mean arterial pressure were slightly higher with EMS than VOL at all exercise intensities reaching 138 (EMS) and 126 bpm (VOL), as well as 148 (EMS) and 137 mmHg (VOL) at 40 W, respectively (P < 0.05). Leg blood flow, oxygen uptake and conductance were similar in the two exercise modes. At 40 W, mean muscle blood flow was close to 200 (range: 165–220) mL 100 g^-1 min^-1, mean peak muscle oxygen uptake reached 230 mL kg^-1 min^-1, and mean conductance became as high as around 45 mL min^-1 mmHg^-1, and normalized for muscle size and arterial pressure it approached 100 mL min^-1 100 g^-1 100 mmHg^-1. Lactate and ammonia efflux from the leg were higher with EMS than with VOL and the difference became larger with increasing exercise intensity (P < 0.05). Muscle glucose uptake was the same in each exercise mode. Femoral venous K⁺ concentration increased with exercise intensity and was higher with EMS than with VOL, reaching 5.1 (EMS) and 4.7 mmol L^-1 (VOL) at 40 W (P < 0.05). The study demonstrates that electrically induced dynamic exercise is associated with a marked cardiovascular response similar to voluntarily performed exercise and a more pronounced activation of the anaerobic metabolism of the muscle. Furthermore, as the electrically activated muscle group is well defined, the present results confirm that peak muscle blood flow can reach 200–250 mL 100 g^-1 min^-1.     

The distensibility of the resistance vessels of skeletal muscle in hypertensive patients

The distensibility of the resistance vessels of skeletal muscle was evaluated in 23 patients with essential arterial hypertension (WSHO grade T-II), and in 14 normotensive control subjects. Five of the hypertensive patients were well treated for over 2 years and 18 were untreated. The ¹³³Xenon wash-out rate from the anterior tibial muscle during reactive hyperemia was recorded before and during an increase of the vascular transmural pressure, brought about by application of a subatmospheric pressure to the leg. At ambient pressure the ¹³³Xenon wash-out rate did not differ between the normotensive and hypertensive subjects, reflecting equal muscle blood flows. However, when the transmural pressure was augmented the ¹³³Xenon wash-out rate in the normotensive subjects increased about twice as much as in the hypertensive patients. This suggests a decreased distensibility of the resistance vessels in hypertensive patients as compared to normotensive subjects, and supports the concept that structural changes of these vessels take place in arterial hypertension. Since the vascular distensibility was equally reduced in the untreated and well treated hypertensive patients it is indicated that the structural changes in the resistance vessels of the leg muscles do not readily decline during antihypertensive treatment.     

Use of selective toxins to separate surface and tubular sodium currents in frog skeletal muscle fibers

The interaction between toxin from the venom of the scorpionTityus serrulatus and sodium channels in skeletal muscle membranes from the frogCaudiverbera caudiverbera was studied. Sodium current from cut sartorius muscle fibers is a complex signal in which early and late components are difficult to separate. External application of Tityus toxin initially blocked the early component in a voltage-dependent manner. Longer exposure to the toxin induced a complete blockade of the two components of the inward current. Application of tetrodotoxin to fibers pretreated with Tityus toxin at submaximal concentrations allowed the observation of the two distinct components of the inward current. Binding of¹²⁵I-labelled toxin to highly purified membrane fractions from the same muscle was used to establish the presence of high affinit receptors both in the transverse-tubular and in the surface membrane.     

Factors affecting SOCE activation in mammalian skeletal muscle fibers

Enzymatically dissociated mouse FDB muscle fibers, loaded with Fura-2 AM, were used to study the effect of mitochondrial uncoupling on the capacitative Ca²⁺ entry, SOCE. Sarcoplasmic reticulum (SR) Ca²⁺ stores were depleted by repetitive exposures to high K⁺ or 4-chloro-m-Cresol (4-CmC) in the absence of extracellular Ca²⁺. SR Ca²⁺ store replenishment was substantially reduced using 5 μM cyclopiazonic acid (CPA). Readmission of external Ca²⁺ (5 mM) increased basal [Ca²⁺]_i under two modalities. In mode 1 [Ca²⁺]_i initially increased at a rate of 0.8 ± 0.1 nM/s and later at a rate of 12.3 ± 2.6 nM/s, reaching a final value of 477.8 ± 36.8 nM in 215.7 ± 25.9 s. In mode 2, [Ca²⁺]_i increased at a rate of 0.8 ± 0.1 nM/s to a value of 204.9 ± 20.6 nM in 185.4 ± 21.1 s. FCCP, 2 μM, reduced this Ca²⁺ entry. In nine FCCP-poisoned fibers, the initial rate of Ca²⁺ increase was 0.34 ± 0.1 nM/s (mean ± SEM), reaching a plateau of 149.2 ± 14.1 nM in 217 ± 19 s. The results may likely be explained by the hypothesis that SOCE is inhibited by mitochondrial uncouplers, pointing to a possible mitochondrial role in its activation. Using time-scan confocal microscopy and the dyes CaOr-5N AM or Rhod-2 AM to label mitochondrial Ca²⁺, we show that during depletion [Ca²⁺]_mito initially increases and later diminishes. Finally, we show that the increase in basal [Ca²⁺]_i, associated with SOCE activation, diminishes upon external Na⁺ withdrawal. Na⁺ entry through the SOCE pathway and activation of the reversal of Na⁺/Ca²⁺ exchanger could explain this SOCE modulation by Na⁺.     

Nucleotide diphosphates activate the ATP-sensitive potassium channel in mouse skeletal muscle

Patch-clamp techniques were used to study the effects of internal nucleotide diphosphates on the K_ATP channel in mouse skeletal muscle. In inside-out patches, application of GDP (100 M) and ADP (100 M) reversibly increased the channel activity. In the presence of internal Mg²⁺ (1 mM), low concentrations of ADP (<300 M) enhanced channel activity and high concentrations of ADP (>300 M) limited channel opening while GDP activated the channel at all concentrations tested. In the absence of internal Mg²⁺, ADP decreased channel activity at all concentrations tested while GDP had no noticeable effect at submillimolar concentrations and inhibited channel activity at millimolar concentrations. GDP [S] (100 M), which behaved as a weak GDP agonist in the presence of Mg²⁺, stimulated ADP-evoked activation whereas it inhibited GDP-evoked activation. The K⁺ channel opener pinacidil was found to activate the K_ATP channel but only in the presence of internal GDP, ADP and GDP [S]. The results are discussed in terms of the existence of multiple nucleotide binding sites, in charge of the regulation of the K_ATP channel.     

Human adipose tissue blood flow during prolonged exercise II

Subcutaneous and perirenal adipose tissue blood flows (ATBF) were measured by the¹³³Xe washout method before, during and after 4 h exercise on a bicycle ergometer. The load corresponded to about 50% of max (i.e. about 1.7l/min). Subcutaneous and perirenal ATBF increased at an average to 3–400 and 700% of their initial control values respectively. In six of nine measuring sites ATBF remained increased in the hour following work. During work plasma glycerol concentrations increased 8 fold. The core temperature increased 0.9°C, skin temperature did not change significantly. During passive elevation of body temperature (core temperature +1.5°C; skin temperature +3°C) neither subcutaneous ATBF nor plasma glycerol concentrations changed significantly. It is concluded that the increase in subcutaneous ATBF during exercise is not a reaction to increased body temperature.     

Inhibitory action of norepinephrine on sodium transport in vascular smooth muscle cells in culture

Cultured vascular smooth muscle cells from porcine aortas incubated in Na⁺-free medium rapidly release their intracellular Na⁺ contents (Na_i) (23±4% of baseline after 60 min incubation, mean ± SEM of 18 experiments). Total Na_i release was inhibited by 35–40% after addition of ouabain and by 60–70% after addition of ouabain + bumetanide. Norepinephrine inhibited ouabain and bumetanide-sensitives Na⁺ efflux with an IC₅₀ of about 10^–9–10^–8 M. Addition of the alpha-adrenergic agonist phenylephrine (10 M) to the cells mimicked the inhibitory action of norepinephrine on Na_i release. Conversely, the beta-adrenergic agonist isoproterenol was without effect on Na_i release. Simultaneous addition of 10 M norepinephrine and the alpha-adrenergic antagonist phentolamine prevented any effect of norepinephrine on the rate of Na_i decline. In A-10 cultured vascular smooth muscle cells, the alpha-adrenergic agonist phenylephrine (10 M) inhibited 40.0±8.1% of ouabain-sensitive Rb⁺ influx and 70.7±6.9% of bumetanide-sensitive Rb⁺ influx (mean ± SEM of three experiments). 50% inhibition of bumetanide-sensitive Rb⁺ influx was obtained with about 5×10^–7 M of phenylephrine. Our results show that in vascular smooth muscle cells a [Na⁺, K⁺, Cl^–]-cotransport system is able to catalyze outward Na⁺ movements (in Na⁺-free media) of a similar order of magnitude to those of the Na⁺, K⁺ pump and that alpha-adrenergic stimulation markedly inhibits Na⁺ efflux (and Rb⁺ influx) through these two transport systems.     

Influence of pH on isometric force development and relaxation in skinned vascular smooth muscle

The effects of pH (from pH values 6.50–7.10) on isometric tension development and relaxation were investigated in Triton X-100 skinned rat caudal artery. Helically cut skinned strips contracted in 21 M Ca²⁺ were studied with respect to maximal isometric tension (P_o) and rate of contraction (T_0.5C), and following relaxation in 18 nm Ca²⁺, the rate of relaxation (T_0.5R). Acidic pH (pH 6.50) decreased P_o to 87% of isometric force obtained at pH 6.90, and increased the rate of contraction as shown by a decrease of T_0.5C to 80%. In contrast, T_0.5R increased 4.5-fold, indicating that with a change of only 0.40 pH units, relaxation rates were dramatically decreased. pCa-tension curves at pH values 6.50, 6.70, 6.90 and 7.10 indicated no significant shift in half maximal activation (pCa₅₀) between pH 6.50 and 6.70, but a significant (P<0.01) shift in pCa₅₀ between pH 6.70 ([Ca²⁺]=0.46 M) and pH 7.10 ([Ca²⁺]=0.87 M). Compared to contractions at pH 6.90, myosin light chain (LC₂₀) phosphorylation at pH 6.50 was significantly greater at 30 and 60 s into contraction but not significantly different at 3–10 min. At both pH 6.50 and 6.90, dephosphorylation was rapid and substantially preceded relaxation; LC₂₀ dephosphorylation and relaxation occurred more rapidly at pH 6.90 than at 6.50. At pH 6.50 and 6.90, relax solutions made with increased Ca²⁺ buffering capacity showed no effect in enhancing T_0.5R, suggesting the difference between relaxation rates was not due to Ca²⁺ diffusion limitations from the skinned strip. We suggest pH changes can after the contractile and relaxation responses in vascular smooth muscle and these effects may be related to LC₂₀ phosphorylation/dephosphorylation regulatory mechanisms.Abbreviations PIPES piperazine-N,N-bis-(2-ethanesulfonic acid) - EGTA 5-ethyleneglycol-bis-(-aminoethyl ether)-N,N,N,N-tetraacetic acid - DTT dithiothreitol - HDTA 1,6-diaminohexane-N,N,N,N-tetraacetic acid - SDS sodium dodecyl sulfate J. P. Gardner was supported in part by an AHA N.J. affiliate postdoctoral fellowship     

The apamin-sensitive potassium current in frog skeletal muscle: its dependence on the extracellular calcium and sensitivity to calcium channel blockers

Slow outward potassium currents were recorded in isolated frog skeletal muscle fibres using the double mannitol-gap voltage-clamp technique.Detubulated fibres failed to generate a slow outward current, and apamin had no effect on the remaining current.The maximum blocking effect of organic and inorganic Ca²⁺-channel blockers on the slow outward channels of intact fibres was larger than that of apamin. Apamin failed to induce an additional block when applied after Ca²⁺-channel blockers.In a low-Ca²⁺ solution (OCa, EGTA 1 mM) the slow outward current was slightly increased and the blocking effect of apamin was enhanced. A Ca²⁺-rich solution (Ca²⁺×10) increased the slow outward current and the blocking effect of apamin was drastically reduced.It is concluded that the apamin-sensitive current which is a component of the slow outward K⁺ current is located in the tubular membrane. Its activation seems barely dependent on the Ca²⁺ influx via the slow inward Ca²⁺ current. Apamin-receptor binding appears to be dependent on the extracellular Ca²⁺ concentration. Blockade of slow outward current by Ca²⁺-channel blockers is likely to be the result of a direct action on the slow K⁺ permeability rather than a consequence of Ca²⁺ channel inhibition.     

Effect of vein pump activation upon muscle blood flow and venous pressure in the human leg

The effect of vein pump activation upon superficial venous pressure and blood flow in human skeletal muscle tissue was studied in 7 healthy subjects. Blood flow was measured in the anterior tibia muscle by the local ¹³³Xe washout technique. The subjects were placed on a steeply tilted couch in nearly erect position. The vein pump in gastroenemius-soleus muscles was activated by heel-raisings. and the anterior tibial muscle remained relaxed during this procedure. Blood flow in the resting anterior tibial muscle was constant before, during and after 20 heel-raisings per min. A more heavy exercise with 40 heel-raisings per min increased blood flow about 100%. This increase in blood flow was absent during venous stasis (40 mmHg), and in areas infiltrated with lidocaine. It is concluded, that intense dynamic exercise in gastrocnemius-soleus muscles, in erect humans, increased blood flow considerably in another crural muscle remaining in the resting state. The present study strongly suggests, that the observed increase in blood flow, was associated with a decrease in regional subfascial venous pressure to below the threshold level of the local sympathetic veno-arteriolar reflex.