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1.
Interstitial cells of Cajal-like cells (ICC-LCs) in the urethra may act as electrical pacemakers of spontaneous contractions. However, their properties in situ and their interaction with neighbouring urethral smooth muscle cells (USMCs) remain to be elucidated. To further explore the physiological role of ICC-LCs, spontaneous changes in [Ca2+ ]i (Ca2+ transients) were visualized in fluo-4 loaded preparations of rabbit urethral smooth muscle. ICC-LCs were sparsely distributed, rather than forming an extensive network. Ca2+ transients in ICC-LCs had a lower frequency and a longer half-width than those of USMCs. ICC-LCs often exhibited Ca2+ transients synchronously with each other, but did not often show a close temporal relationship with Ca2+ transients in USMCs. Nicardipine (1 μ m ) suppressed Ca2+ transients in USMCs but not in ICC-LCs. Ca2+ transients in ICC-LCs were abolished by cyclopiazonic acid (10 μ m ), ryanodine (50 μ m ) and caffeine (10 m m ) or by removing extracellular Ca2+ , and inhibited by 2-aminoethoxydiphenyl borate (50 μ m ) and 3-morpholino-sydnonimine (SIN-1; 10 μ m ), but facilitated by increasing extracellular Ca2+ or phenylephrine (1–10 μ m ). These results indicated that Ca2+ transients in urethral ICC-LCs in situ rely on both Ca2+ release from intracellular Ca2+ stores and Ca2+ influx through non-L-type Ca2+ channel pathways. ICC-LCs may not act as a coordinated pacemaker electrical network as do ICC in the gastrointestinal (GI) tract. Rather they may randomly increase excitability of USMCs to maintain the tone of urethral smooth muscles. 相似文献
2.
Two distinct populations of interstitial cells of Cajal (ICC) exist within the tunica muscularis of the gastric antrum, and these cells serve different physiological functions. One population of ICC generates and actively propagates electrical slow waves, and the other population of ICC is innervated by excitatory and inhibitory motor neurons and mediates enteric motor neurotransmission. In spite of the key role of ICC in gastric excitability, little is known about the ionic conductances that underlie the functional diversity of these cells. In the present study we isolated ICC from the murine gastric antrum and investigated the Ca2+ -dependent ionic conductances expressed by these cells using the patch clamp technique. Conductances in ICC were compared with those expressed in smooth muscle cells. The cells studied were identified by RT-PCR using cell-specific primers that included Myh11 (smooth muscle cells), Kit (ICC) and Uchl1 (enteric neurons) following electrophysiolgical recordings. Distinct ionic conductances were observed in Kit-positive cells. One group of ICC expressed a basal non-selective cation conductance (NSCC) that was inhibited by an increase in [Ca2+ ]i in a calmodulin (CaM)-dependent manner. A second population of ICC generated spontaneous transient inward currents (STICs) and expressed a basal noisy NSCC that was facilitated by an increase in [Ca2+ ]i in a CaM-dependent manner. The [Ca2+ ]i -facilitated NSCC in ICC was blocked by the Cl− channel antagonists 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), anthracene-9-carboxylate (9-AC) and niflumic acid. These data suggest that distinct NSCC are expressed in subpopulations of ICC and these conductances may underlie the functional differences of these cells within the gastric antrum. 相似文献
3.
G. D. S. Hirst N. J. Bramich N. Teramoto H. Suzuki† F. R. Edwards 《The Journal of physiology》2002,540(3):907-919
Regenerative potentials were initiated by depolarizing short segments of single bundles of circular muscle isolated from the gastric antrum of guinea-pigs. When changes in [Ca2+ ]i and membrane potential were recorded simultaneously, regenerative potentials were found to be associated with an increase in [Ca2+ ]i , with the increase starting after a minimum latency of about 1 s. Although the increase in [Ca2+ ]i was reduced by nifedipine, the amplitudes of the regenerative responses were little changed. Regenerative responses and associated changes in [Ca2+ ]i were abolished by loading the preparations with the Ca2+ chelator MAPTA-AM. Regenerative potentials were abolished by 2-aminoethoxydiphenyl borate (2APB), an inhibitor of IP3 induced Ca2+ release, by N -ethylamaleimide (NEM), an alkylating agent which blocks activation of G-proteins and were reduced in amplitude by two agents which block chloride (Cl− )-selective channels in many tissues. The observations suggest that membrane depolarization triggers IP3 formation. This causes Ca2+ release from intracellular stores which activates Ca2+ -dependent Cl− channels. 相似文献
4.
5.
Discrete store-operated calcium influx into an intracellular compartment in rabbit arteriolar smooth muscle 总被引:1,自引:3,他引:1
This study tested the hypothesis that store-operated channels (SOCs) exist as a discrete population of Ca2+ channels activated by depletion of intracellular Ca2+ stores in cerebral arteriolar smooth muscle cells and explored their direct contractile function. Using the Ca2+ indicator fura-PE3 it was observed that depletion of sarcoplasmic reticulum (SR) Ca2+ by inhibition of SR Ca2+ -ATPase (SERCA) led to sustained elevation of [Ca2+ ]i that depended on extracellular Ca2+ and slightly enhanced Mn2+ entry. Enhanced background Ca2+ influx did not explain the raised [Ca2+ ]i in response to SERCA inhibitors because it had marked gadolinium (Gd3+ ) sensitivity, which background pathways did not. Effects were not secondary to changes in membrane potential. Thus SR Ca2+ depletion activated SOCs. Strikingly, SOC-mediated Ca2+ influx did not evoke constriction of the arterioles, which were in a resting state. This was despite the fura-PE3-indicated [Ca2+ ]i rise being greater than that evoked by 20 m m [K+ ]o (which did cause constriction). Release of endothelial vasodilators did not explain the absence of SOC-mediated constriction, nor did a change in Ca2+ sensitivity of the contractile proteins. We suggest SOCs are a discrete subset of Ca2+ channels allowing Ca2+ influx into a 'non-contractile' compartment in cerebral arteriolar smooth muscle cells. 相似文献
6.
Calcium events in smooth muscles and their interstitial cells; physiological roles of sparks 总被引:2,自引:1,他引:2
Tom B. Bolton 《The Journal of physiology》2006,570(1):5-11
The observation of spontaneous sporadic releases of packets of stored calcium made 20 years ago has opened up a number of new concepts in smooth muscle physiology: (1) the calcium release sites are ryanodine and inositol 1,4,5-trisphosphate (IP3 ) receptor channels which contribute to cell-wide increases in [Ca2 + ]i in response to cell depolarization, activation of IP3 -generating receptors, or other stimuli; (2) changes in [Ca2 + ]i act back on the cell membrane to activate or modulate K+ , Cl− and cation channel activity so affecting contraction, in arterial smooth muscle for example affecting blood pressure; (3) IP3 production is voltage dependent and is believed to contribute to pacemaker potentials and to refractory periods which control the rhythmical motility of many hollow organs. Most smooth muscle tissues contain interstitial cells (ICs) in addition to contractile smooth muscle cells (SMCs). The interactions of these internal mechanisms, and in turn the interactions of SMCs and ICs in various smooth muscle tissues, are major factors in determining the unique physiological profiles of individual smooth muscles. 相似文献
7.
Pasi Tavi David G. Allen Perttu Niemelä† Olli Vuolteenaho‡ Matti Weckström† Håkan Westerblad 《The Journal of physiology》2003,551(1):5-12
Activation of the contractile machinery in skeletal muscle is initiated by the action-potential-induced release of Ca2+ from the sarcoplasmic reticulum (SR). Several proteins involved in SR Ca2+ release are affected by calmodulin kinase II (CaMKII)-induced phosphorylation in vitro , but the effect in the intact cell remains uncertain and is the focus of the present study. CaMKII inhibitory peptide or inactive control peptide was injected into single isolated fast-twitch fibres of mouse flexor digitorum brevis muscles, and the effect on free myoplasmic [Ca2+ ] ([Ca2+ ]i ) and force during different patterns of stimulation was measured. Injection of the inactive control peptide had no effect on any of the parameters measured. Conversely, injection of CaMKII inhibitory peptide decreased tetanic [Ca2+ ]i by ≈25 %, but had no significant effect on the rate of SR Ca2+ uptake or the force-[Ca2+ ]i relationship. Repeated tetanic stimulation resulted in increased tetanic [Ca2+ ]i , and this increase was smaller after CaMKII inhibition. In conclusion, CaMKII-induced phosphorylation facilitates SR Ca2+ release in the basal state and during repeated contractions, providing a positive feedback between [Ca2+ ]i and SR Ca2+ release. 相似文献
8.
Clathrin-mediated endocytosis in snake motor terminals is directly facilitated by intracellular Ca2+
At the snake neuromuscular junction, low temperature (LT, 5–7°C) blocks clathrin-mediated endocytosis (CME) while exocytosis is largely unaffected. Thus compensatory endocytosis that normally follows transmitter release is inhibited, or 'delayed' until the preparation is warmed to room temperature (RT). This delay was exploited to observe how changes in bulk [Ca2+ ]i directly affect CME. Motor terminals were loaded with fura-2 to monitor [Ca2+ ]i . With brief stimulation at LT, [Ca2+ ]i transiently increased but returned to baseline (∼63 n m ) in < 8 min. After 15 min at LT, [Ca2+ ]i was altered by incubating preparations in the Ca2+ ionophore ionomyocin. Preparations were then warmed to RT to initiate delayed endocytosis, which was quantified as uptake of the fluorescent optical probe sulforhodamine 101. Endocytosis was more rapid when [Ca2+ ]i increased; the rate at 300 n m Ca2+ was ∼double that under basal conditions. Thus the rate of CME – isolated from stimulation, transmitter release, and other forms of endocytosis – is directly influenced by intraterminal Ca2+ . 相似文献
9.
Capacitative calcium entry supports calcium oscillations in human embryonic kidney cells 总被引:4,自引:4,他引:4
Treatment of human epithelial kidney (HEK293) cells with low concentrations of the muscarinic agonist methacholine results in the activation of complex and repetitive cycling of intracellular calcium ([Ca2+ ]i ), known as [Ca2+ ]i oscillations. These oscillations occur with a frequency that depends on the concentration of methacholine, whereas the magnitude of the [Ca2+ ]i spikes does not. The oscillations do not persist in the absence of extracellular Ca2+ , leading to the conclusion that entry of Ca2+ across the plasma membrane plays a significant role in either their initiation or maintenance. However, treatment of cells with high concentrations of GdCl3 , a condition which limits the flux of calcium ions across the plasma membrane in both directions, allows sustained [Ca2+ ]i oscillations to occur. This suggests that the mechanisms that both initiate and regenerate [Ca2+ ]i oscillations are intrinsic to the intracellular milieu and do not require entry of extracellular Ca2+ . This would additionally suggest that, under normal conditions, the role of calcium entry is to sustain [Ca2+ ]i oscillations. By utilizing relatively specific pharmacological manoeuvres we provide evidence that the Ca2+ entry that supports Ca2+ oscillations occurs through the store-operated or capacitative calcium entry pathway. However, by artificial introduction of a non-store-operated pathway into the cells (TRPC3 channels), we find that other Ca2+ entry mechanisms can influence oscillation frequency in addition to the store-operated channels. 相似文献
10.
Kawakami M Nagira T Hayashi T Shimamoto C Kubota T Mori H Yoshida H Nakahari T 《Experimental physiology》2004,89(6):739-751
The ciliary beat frequency (CBF) of rat tracheal ciliary cells in a slice preparation was measured using video-enhanced contrast (VEC) microscopy. Acetylcholine (ACh) increased CBF mediated via intracellular Ca2+ concentration ([Ca2+ ]i ) in a dose-dependent manner. An adequate hypo-osmotic stress (−40 mos m ) potentiated ACh-stimulated CBF increase in tracheal ciliary cells and shifted the ACh dose–response curve to the left (lower concentration side). This potentiation was independent of hypo-osmotic stresses applied ranging from −20 mosM to −90 mosM. A hypo-osmotic stress induces ATP release in many cell types. The present study demonstrated that suramin (an inhibitor of purinergic receptors) and apyrase (an ATPase/ADPase) eliminate the hypo-osmotic potentiation of ACh-stimulated CBF increase and that ATP increased [Ca2+ ]i and CBF, as well as potentiating ACh-stimulated rises in [Ca2+ ]i and CBF increase. Moreover, the apical surface of tracheal ciliary cells were stained immunopositive for the P2X4 purinergic receptor. A hypo-osmotic stress (−40 mosM) transiently increased [Ca2+ ]i and potentiated the ACh-stimulated [Ca2+ ]i increase. The hypo-osmotic potentiation of ACh-stimulated CBF increase was not detected under Ca2+ -free conditions. These observations suggest that a hypo-osmotic stress stimulates ATP release from the trachea. The released ATP may induce further increases in [Ca2+ ]i and CBF in ACh-stimulated tracheal ciliary cells, which may be mediated by purinergic receptors, such as P2X4 . 相似文献
11.
Rat peritoneal mast cells purified on a Percoll gradient were loaded with the fluorescent Ca2+ indicator fura-2 and were challenged with different concentrations of substance P (SP), and intracellular calcium concentrations ([Ca2+ ]i ) were measured by a spectrofluorometric assay. SP at 5 × 10−6 mol/1 and 10−5 mol/1 caused a significant histamine release with a significant increase in [Ca2+ ]i in a dose-dependent manner. However, SP at 10−8 -10−6 mol/1 did not induce either histamine release or increase in [Ca2+ ]i . Extracellular calcium at 0.9 mM inhibited the histamine release with a significant reduction of [Ca2+ ]i compared with that of the cells in a nominally calcium-free condition. These results indicate that the action of SP on rat mast cells relies upon [Ca2+ ]i to induce histamine release. 相似文献
12.
Spontaneous [Ca2+ ]i transients were measured in the mouse neocortex from embryonic day 16 (E16) to postnatal day 6 (P6). On the day of birth (P0), cortical neurones generated widespread, highly synchronous [Ca2+ ]i transients over large areas. On average, 52% of neurones participated in these transients, and in 20% of slices, an average of 80% participated. These transients were blocked by TTX and nifedipine, indicating that they resulted from Ca2+ influx during electrical activity, and occurred at a mean frequency of 0.91 min−1 . The occurrence of this activity was highly centred at P0: at E16 and P2 an average of only 15% and 24% of neurones, respectively, participated in synchronous transients, and they occurred at much lower frequencies at both E16 and P2 than at P0. The overall frequency of [Ca2+ ]i transients in individual cells did not change between E16 and P2, just the degree of their synchronicity. The onset of this spontaneous, synchronous activity correlated with a large increase in Na+ current density that occurred just before P0, and its cessation with a large decrease in resting resistance that occurred just after P2. This widespread, synchronous activity may serve a variety of functions in the neonatal nervous system. 相似文献
13.
Barbara Wedel Rebecca R. Boyles James W. Putney Jr Gary S. Bird 《The Journal of physiology》2007,579(3):679-689
We have investigated the nature of the Ca2+ entry supporting [Ca2+ ]i oscillations in human embryonic kidney (HEK293) cells by examining the roles of recently described store-operated Ca2+ entry proteins, Stim1 and Orai1. Knockdown of Stim1 by RNA interference (RNAi) reduced the frequency of [Ca2+ ]i oscillations in response to a low concentration of methacholine to the level seen in the absence of external Ca2+ . However, knockdown of Stim1 did not block oscillations in canomical transient receptor potential 3 channel (TRPC3)-expressing cells and did not affect Ca2+ entry in response to arachidonic acid. The effects of knockdown of Stim1 could be reversed by inhibiting Ca2+ extrusion with a high concentration of Gd3+ , or by rescuing the knockdown by overexpression of Stim1. Similarly, knockdown of Orai1 abrogated [Ca2+ ]i oscillations, and this was reversed by use of high concentrations of Gd3+ ; however, knockdown of Orai1 did not affect arachidonic acid-activated entry. RNAi targeting 34 members of the transient receptor potential (TRP) channel superfamily did not reveal a role for any of these channel proteins in store-operated Ca2+ entry in HEK293 cells. These findings indicate that the Ca2+ entry supporting [Ca2+ ]i oscillations in HEK293 cells depends upon the Ca2+ sensor, Stim1, and calcium release-activated Ca2+ channel protein, Orai1, and provide further support for our conclusion that it is the store-operated mechanism that plays the major role in this pathway. 相似文献
14.
Streptomycin and intracellular calcium modulate the response of single guinea-pig ventricular myocytes to axial stretch 总被引:7,自引:0,他引:7
We tested the hypothesis that both stretch-activated channels (SACs) and intracellular calcium ([Ca2+ ]i ) are important in the electrical response of single guinea-pig ventricular myocytes to axial stretch. Myocytes were attached to carbon fibre transducers and stretched, sarcomere length increased by approximately 9 %, and there was a prolongation of the action potential duration. Streptomycin, a blocker of SACs, had no effect upon the shortening, [Ca2+ ]i transients or action potentials of electrically stimulated, unstretched myocytes, at a concentration of 50 μ m , but at 40 μ m , prevented any stretch-induced increase in action potential duration. Under action potential clamp, stretch elicited a current with a linear current-voltage relationship that was inward at membrane potentials negative to its reversal potential of −30 mV, in 10 of 24 cells tested, and was consistent with the activation of non-specific, cationic SACs. This current was not seen in any stretched cells that were exposed to 40 μ m streptomycin. However, exposure of cells to 5 μ m BAPTA-AM, in order to reduce [Ca2+ ]i transients, also abolished stretch-induced prolongation of the action potential. We conclude that both SACs and [Ca2+ ]i are important in the electrical response of cardiac myocytes to stretch, and propose that stretch-induced changes in electrical activity and [Ca2+ ]i may be linked by inter-dependent mechanisms. 相似文献
15.
Microheterogeneity of calcium signalling in dendrites 总被引:2,自引:0,他引:2
Lucas D. Pozzo-Miller† John A. Connor‡ S. Brian Andrews†§ 《The Journal of physiology》2000,525(1):53-61
Transient changes in the intracellular concentration of free Ca2+ ([Ca2+ ]i ) originating from voltage- or ligand-gated influx and by ligand- or Ca2+ -gated release from intracellular stores, trigger or modulate many fundamental neuronal processes, including neurotransmitter release and synaptic plasticity. Of the intracellular compartments involved in Ca2+ clearance, the endoplasmic reticulum (ER) has received the most attention because it expresses Ca2+ pumps and Ca2+ channels, thus endowing it with the potential to act as both an intracellular calcium sink and store. We review here our ongoing work on the role of calcium sequestration into, and release from, ER cisterns and the role that this plays in the generation and termination of free [Ca2+ ]i transients in dendrites of pyramidal neurons in hippocampal slices during and after synaptic activity. These studies have been approached by combining parallel microfluorometric measurements of free cytosolic [Ca2+ ]i transients with energy-dispersive X-ray microanalytical measurements of total Ca content within specific dendritic compartments at the electron microscopy level. Our observations support the emerging realization that specific subsets of dendritic ER cisterns provide spatial and temporal microheterogeneity of Ca2+ signalling, acting not only as a major intracellular Ca sink involved in active clearance mechanisms after voltage- and ligand-gated Ca2+ influx, but also as an intracellular Ca2+ source that can be mobilized by a signal cascade originating at activated synapses. 相似文献
16.
Keith W. Dilly Charles F. Rossow V. Scott Votaw James S. Meabon Jennifer L. Cabarrus Luis F. Santana 《The Journal of physiology》2006,572(1):227-241
Ca2+ release during excitation–contraction (EC) coupling varies across the left ventricular free wall. Here, we investigated the mechanisms underlying EC coupling differences between mouse left ventricular epicardial (Epi) and endocardial (Endo) myocytes. We found that diastolic and systolic [Ca2+ ]i was higher in paced Endo than in Epi myocytes. Our data indicated that differences in action potential (AP) waveform between Epi and Endo cells only partially accounted for differences in [Ca2+ ]i . Rather, we found that the amplitude of the [Ca2+ ]i transient, but not its trigger – the Ca2+ current – was larger in Endo than in Epi cells. We also found that spontaneous Ca2+ spark activity was about 2.8-fold higher in Endo than in Epi cells. Interestingly, ryanodine receptor type 2 (RyR2) protein expression was nearly 2-fold higher in Endo than in Epi myocytes. Finally, we observed less Na+ –Ca2+ exchanger function in Endo than in Epi cells, which was associated with decreased Ca2+ efflux during the AP; this contributed to higher diastolic [Ca2+ ]i and SR Ca2+ in Endo than in Epi cells during pacing. We propose that transmural differences in AP waveform, SR Ca2+ release, and Na+ –Ca2+ exchanger function underlie differences in [Ca2+ ]i and EC coupling across the left ventricular free wall. 相似文献
17.
Single channel properties of Ca2+ -activated K+ (BK or Maxi-K) channels have been investigated in presynaptic membranes in Xenopus motoneurone–muscle cell cultures. The occurrence and density of BK channels increased with maturation/synaptogenesis and was not uniform: highest at the release face of bouton-like synaptic varicosities in contact with muscle cells, and lowest in varicosities that did not contact muscle cells. The Ca2+ affinity of the channel ( K d = 7.7 μ m at a membrane potential of +20 mV) was lower than those of BK channels that have been characterized in other terminals. Hill coefficients varied between 1.5 and 2.8 at different potentials and open probability increased e-fold per 16 mV change in membrane potential over a range of [Ca2+ ]i from 1 μ m to 1 m m . The maximal activation rate of ensembled single BK channel currents was in the submillisecond range at ≥+20 mV. The activation rate increased ∼10-fold in response to a [Ca2+ ]i increase from 1 to 100 μ m , but increased only ∼2-fold with a voltage change from +20 to +130 mV. The fastest activation kinetics of BK channels in cell-attached patches resembled that in inside-out patches with [Ca2+ ]i of 100 μ m or more, suggesting that many BK channels are located very close to calcium channels. Given the low Ca2+ affinity and rapid Ca2+ binding/unbinding properties, we conclude that BK channels in this preparation are adapted to play an important role in regulation of neurotransmitter release, and they are ideal reporters of local [Ca2+ ] at the inner membrane surface. 相似文献
18.
Calmodulin (CaM) binds to KCNQ2–4 channels within their carboxy termini, where it regulates channel function. The existing data have not resolved the Ca2+ dependence of the interaction between the channels and CaM. We performed glutathione S-transferase (GST)-pull-down assays between purified KCNQ2–4 carboxy termini and CaM proteins to determine the Ca2+ dependence of the interaction in vitro . The assays showed substantial Ca2+ dependence of the interaction of the channels with wild-type (WT) CaM, but not with dominant-negative (DN) CaM. To demonstrate CaM–channel interactions in individual living cells, we performed fluorescence resonance energy transfer (FRET) between ECFP-tagged KCNQ2–4 channels and EYFP-tagged CaM expressed in CHO cells, performed under total internal reflection fluorescence (TIRF) microscopy, in which excitation light only penetrates several hundred nanometres into the cell, thus isolating membrane events. FRET was assayed between the channels and either WT or DN CaM, performed under conditions of normal [Ca2+ ]i , low [Ca2+ ]i or high [Ca2+ ]i induced by empirically optimized bathing solutions. The FRET data suggest a strong Ca2+ dependence for the interaction between WT CaM and KCNQ2, but less so for KCNQ3 and KCNQ4. FRET between all KCNQ2–4 channels and DN CaM was robust, and not significantly Ca2+ dependent. These data show interactions between CaM and KCNQ channels in living cells, and suggest that the interactions between KCNQ2–4 channels and CaM are likely to have Ca2+ -dependent and Ca2+ -independent components. 相似文献
19.
Niels Ødum Paul J. Martin Gary L. Schieven Susan Masewicz John A. Hansen Jeffrey A. Ledbetter 《Tissue antigens》1991,38(3):72-77
Abstract: Crosslinking HLA-DR molecules by monoclonal antibodies (mAb) induces protein tyrosine phosphorylation and results in a secondary elevation of free cytoplasmic Ca2+ concentration ([Ca2+ ]i ) in activated human T cells. Here we have studied the effect of DR on CD3-induced signal transduction in allospecific T-cell clones and T-leukemia (HUT78) cells. Co-crosslinking of DR with CD3 produced an enhanced [Ca2+ ]i response compared to that seen with CD3 alone. In contrast, CD2 responses were not enhanced by co-crosslinking with DR. Co-crosslinking CD45 in a tri-molecular complex of CD45, CD3, and DR completely abrogated the enhancing effects of DR on CD3-induced [Ca2+ ]i responses. In contrast, the enhancing effect of co-crosslinking CD4 on CD3 responses was not inhibited by co-crosslinking CD45. Thus, the DR-mediated accessory signals appear to be regulated differently from those provided by CD4 accessory molecules. The present data confirm, at the level of second messengers, recent findings suggesting that DR molecules have accessory functions in CD3/Ti-mediated T-cell responses. 相似文献
20.
Morphological and physiological evidence for interstitial cell of Cajal-like cells in the guinea pig gallbladder 总被引:6,自引:0,他引:6
Brigitte Lavoie Onesmo B. Balemba Mark T. Nelson Sean M. Ward Gary M. Mawe 《The Journal of physiology》2007,579(2):487-501
Gallbladder smooth muscle (GBSM) exhibits spontaneous rhythmic electrical activity, but the origin and propagation of this activity are not understood. We used morphological and physiological approaches to determine whether interstitial cells of Cajal (ICC) are present in the guinea pig extrahepatic biliary tree. Light microscopic studies involving Kit tyrosine kinase immunohistochemistry and laser confocal imaging of Ca2+ transients revealed ICC-like cells in the gallbladder. One type of ICC-like cell had elongated cell bodies with one or two primary processes and was observed mainly along GBSM bundles and nerve fibres. The other type comprised multipolar cells that were located at the origin and intersection of muscle bundles. Electron microscopy revealed ICC-like cells that were rich in mitochondria, caveolae and smooth endoplasmic reticulum and formed close appositions between themselves and with GBSM cells. Rhythmic Ca2+ flashes, which represent Ca2+ influx during action potentials, were synchronized in any given GBSM bundle and associated ICC-like cells. Gap junction uncouplers (1-octanol, carbenoxolone, 18β-glycyrrhetinic acid and connexin mimetic peptide) eliminated or greatly reduced Ca2+ flashes in GBSM, but they persisted in ICC-like cells, whereas the Kit tyrosine kinase inhibitor, imanitib mesylate, eliminated or reduced action potentials and Ca2+ flashes in both cell types, as well as associated tissue contractions. This study provides morphological and physiological evidence for the existence of ICC-like cells in the gallbladder and presents data supporting electrical coupling between ICC-like and GBSM cells. The results support a role for ICC-like cells in the generation and propagation of spontaneous rhythmicity, and hence, the excitability of gallbladder. 相似文献