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101.
Babak S. Jahromi Yasuo Aihara Jinglu Ai Zhen-Du Zhang George Weyer Elena Nikitina Reza Yassari Khaled M. Houamed R. Loch Macdonald 《Neuroscience letters》2008
The pathogenesis of cerebral vasospasm after subarachnoid haemorrhage (SAH) involves sustained contraction of arterial smooth muscle cells that is maximal 6–8 days after SAH. We reported that function of voltage-gated K+ (KV) channels was significantly decreased during vasospasm 7 days after SAH in dogs. Since arterial constriction is regulated by membrane potential that in turn is determined predominately by K+ conductance, the compromised K+ channel dysfunction may cause vasospasm. Additional support for this hypothesis would be demonstration that K+ channel dysfunction is temporally coincident with vasospasm. To test this hypothesis, SAH was created using the double haemorrhage model in dogs and smooth muscle cells from the basilar artery, which develops vasospasm, were isolated 4 days (early vasospasm), 7 days (during vasospasm) and 21 days (after vasospasm) after SAH and studied using patch-clamp electrophysiology. We investigated the two main K+ channels (KV and large-conductance voltage/Ca2+-activated (KCa) channels). Electrophysiologic function of KCa channels was preserved at all times after SAH. In contrast, function of KV channels was significantly decreased at all times after SAH. The decrease in cell size and degree of KV channel dysfunction was maximal 7 days after SAH. The results suggest that KV channel dysfunction either only partially contributes to vasospasm after SAH or that compensatory mechanisms develop that lead to resolution of vasospasm before KV channels recover their function. 相似文献
102.
R. Wang Lingyun Wu Zunzhe Wang 《Pflügers Archiv : European journal of physiology》1997,434(3):285-291
The vasorelaxation induced by carbon monoxide (CO) has been demonstrated previously. Both a guanosine cyclic monophosphate
(cGMP) signalling pathway and cGMP-independent mechanisms have been proposed to be responsible for the vascular action of
CO. A direct effect of CO on the activity of calcium-activated K (KCa) channels in vascular smooth muscle cells (SMCs) and the underlying mechanisms were investigated in the present study. It
was found that CO hyperpolarized single SMCs isolated from rat tail arteries. The whole-cell outward K+ channel currents in vascular SMCs, but not in neuroblastoma cells, were enhanced by CO. Extracellularly or intracellularly
applied CO increased the open probability of single high-conductance KCa channels concentration-dependently without affecting the single channel conductance. Although it did not increase the resting
level of intracellular free calcium concentration, CO significantly enhanced the calcium sensitivity of single KCa channels in SMCs. Furthermore, the effect of CO on KCa channels was not mediated by cGMP or guanine nucleotide-binding proteins (G proteins, Gi/Go or Gs) in excised membrane patches. Our results suggest that the direct modulation of high-conductance KCa channels in vascular SMCs by CO may constitute a novel mechanism for the vascular effect of CO.
Received: 9 January 1997 / Received after revision: 21 February 1997 / Accepted: 10 March 1997 相似文献
103.
Schaefer M 《Pflügers Archiv : European journal of physiology》2005,451(1):35-42
Mammalian homologues of the Drosophila melanogaster transient receptor potential (TRP) channels are the second largest cation channel family within the superfamily of hexahelical cation channels. Most mammalian TRP channels function as homooligomers and mediate mono- or divalent cation entry upon activation by a variety of stimuli. Because native TRP channels may be multimeric proteins of possibly complex composition, it is difficult to compare cation conductances in native tissues to those of clearly defined homomeric TRP channel complexes in living cells. Therefore, the possibility of heteromeric TRP channel assembly has been investigated in recent years by several groups. As a major conclusion of these studies, most heteromeric TRP channel complexes appear to consist of subunit combinations only within relatively narrow confines of phylogenetic subfamilies. Although the general capability of heteromer formation between closely related TRP channel subunits is now clearly established, we are only beginning to understand whether these heteromeric complexes are of physiological significance. This review summarizes the current knowledge on the promiscuity and specificity of the assembly of channel complexes composed of TRPC-, TRPV- and TRPM-subunits of mammalian TRP channels. 相似文献
104.
目的: 研究心肌肽素对豚鼠心室肌细胞钠通道的影响,探讨心肌肽素在离子通道水平的作用机制。 方法: 用急性酶解分离法获得豚鼠心室肌细胞,标准全细胞膜片钳技术记录钠电流(INa)。 结果: 心肌肽素1、5、10、50、100、500 mg/L使豚鼠心室肌细胞INa分别减少(0±1)%、(6±2)%、(10±2)%、(15±1)%、(22±9)%、(30±6)%,呈浓度依赖性抑制INa。心肌肽素50 mg/L使INa激活时间(TTP)从(2.8±0.7) ms延长至(3.0±0.8) ms (P<0.05);使INa电流密度-电压曲线上移,但不改变激活电位、峰电位、反转电位和I-V曲线的形状;不影响稳态激活曲线、稳态失活曲线和稳态失活后恢复曲线。 结论: 心肌肽素浓度依赖性抑制豚鼠心室肌细胞INa,可能是其抗心律失常作用的机制之一。 相似文献
105.
Alfonso Araque Washington Buño 《Pflügers Archiv : European journal of physiology》1995,430(4):541-551
The early outward current in opener muscle fibres of crayfish (Procambarus clarkii) was studied using the two-electrode voltage-clamp technique. This current was abolished in Ca2+-free and 5 mM Cd2+ solutions, and was blocked by extra- or intracellular tetraethylammonium, indicating that it was a Ca2+-dependent K+ current [I
K(Ca)]. I
K(Ca) was voltage dependent, apamin insensitive and sensitive to charybdotoxin (CTX), which, in addition to its tetraethylammonium sensitivity, suggests that the channels mediating I
K(Ca) behave in a BK type manner. I
K(Ca) activation was extremely fast, reaching a maximum within 5 ms, and the inactivation was incomplete, stabilizing at a persistent steady-state. I
K(Ca) was insensitive to intracellular ethylenebis(oxonitrilo)tetraacetate (EGTA), but was abolished by injection of the faster Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N,N'-tetraacetic acid (BAPTA), suggesting that voltage-dependent Ca2+ channels and those mediating I
K(Ca) should be clustered closely on the membrane. Under two-electrode current-clamp recording mode, low amplitude, graded responses were evoked under control conditions, whereas repetitive all-or-none spikes were elicited by application of CTX or after loading the cells with BAPTA. We conclude that I
K(Ca) activates extremely quickly, is persistent and is responsible for the generation and control of the low amplitude, graded, active responses of opener muscle fibres. 相似文献
106.
TRP(Transient receptor potentical)家族是非选择性阳离子通道家族,近来发现其与肾脏关系密切,如调节肾小管离子转运,肾脏微循环等。TRP通道异常可导致遗传性局灶节段硬化性肾病(FSGS),常染色体显性遗传多囊肾(ADPKD),低镁血症继发低钙血症(HSH)等,对TRP通道的进一步研究将有助于临床肾脏病的防治。 相似文献
107.
M. Toselli Patrizia Tosetti Vanni Taglietti 《Pflügers Archiv : European journal of physiology》1997,433(5):587-596
Ca2+ channel modulation by the μ opioid agonist [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAGO) and the δ opiate agonists [d-Pen2, d-Pen5]-enkephalin (DPDPE) and [d-Ala2, d-Leu5]-enkephalin (DADLE) in cultured human neuroblastoma SH-SY5Y cells was investigated using the whole-cell variant of the patch-clamp
technique. In SH-SY5Y cells, differentiated in vitro with retinoic acid, all agonists reversibly decreased high-voltage-activated,
ω-conotoxin-sensitive Ba2+ currents in a concentration-dependent way. Inhibition was maximal with a 1 μM concentration of opiate agonists (76% with DAGO
and 63% with δ agonists, when measured at 0 mV) and was characterized by a clear slow down of Ba2+ current activation at low test potentials. Both inhibition and slow down of activation were attenuated at more positive potentials,
and could be partially relieved by strong conditioning depolarizations. Current suppression operated by both μ and δ agonists
was prevented by pre-treatment of the cells with pertussis toxin. No sign of additivity was observed when δ agonists were
applied to cells that were maximally activated by DAGO, suggesting that a common mechanism, involving the same type of modulating
molecule, is responsible for Ca2+ channel inhibition promoted by activation of μ and δ opioid receptors in SH-SY5Y cells.
Received: 10 October 1996 / Received after revision and accepted: 18 November 1996 相似文献
108.
Arnaldo Ferroni A. Galli M. Mazzanti 《Pflügers Archiv : European journal of physiology》1996,431(6):954-963
Neuronal cell firing is crucial to nerve-nerve communication. The ability to produce consecutive action potentials is related
to the activation of inward currents after each upstroke. If fast Na current is indeed responsible for the overshoot, it is
still unclear which current drives membrane voltage to the Na threshold. In this study we present evidence that in adult rat
sensory neurones a dihydropyridine-sensitive Ca channel exists in addition to the well characterized L-type, or high-threshold
Ca channel. During stimulated action potential trains, L-type Ca channels open during the excitation wave, whereas activity
of the other dihydropyridine-sensitive Ca channel was observed primarily between action potentials. This second Ca pathway
shows remarkably long openings at negative potentials after a series of positive prepulses. The nerve action potential and
the repetitive firing work as a physiological Ca channel facilitation mechanism. Therefore, we suggest that this novel Ca
conductance provides inward current, between two consecutive action potentials, able to modulate the frequency of neuronal
bursts.
Received: 3 August 1995/Received after revision: 9 October 1995/Accepted: 10 October 1995 相似文献
109.
Fiona Murray Paul A. Insel Jason X.-J. Yuan 《Respiratory physiology & neurobiology》2006,151(2-3):192
High altitude pulmonary edema (HAPE) is a potentially fatal complication in response to exposure to low O2 at high altitudes. Hypoxia, by causing pulmonary vasoconstriction, increases pulmonary vascular resistance and pulmonary arterial pressure, both of which are features in the pathogenesis of HAPE. Uneven hypoxic pulmonary vasoconstriction is thought to be responsible for increased capillary pressure and leakage, resulting in edema. O2-sensitive ion channels are known to play pivotal roles in determining vascular tone in response to hypoxia. K+, Ca2+ and Na+ channels are ubiquitously expressed in both endothelial and smooth muscle cells of the pulmonary microvasculature, subfamilies of which are regulated by local changes in PO2. Hypoxia reduces activity of voltage-gated K+ channels and down-regulates their expression leading to membrane depolarization, Ca2+ influx in pulmonary artery smooth muscle cells (by activating voltage-dependent Ca2+ channels) and vasoconstriction. Hypoxia up-regulates transient receptor potential channels (TRPC) leading to enhanced Ca2+ entry through receptor- and store-operated Ca2+ channels. Altered enrichment of ion channels in membrane microdomains, in particular in caveolae, may play a role in excitation–contraction coupling and perhaps in O2-sensing in the pulmonary circulation and thereby may contribute to the development of HAPE. We review the role of ion channels, in particular those outlined above, in response to low O2 on vascular tone and pulmonary edema. Advances in the understanding of ion channels involved in the physiological response to hypoxia should lead to a greater understanding of the pathogenesis of HAPE and perhaps in the identification of new therapies. 相似文献
110.
Martin Diener Marko Bertog Michael Fromm Erwin Scharrer 《Pflügers Archiv : European journal of physiology》1996,432(2):293-300
The effect of cell swelling induced by hypotonic media was studied in segments of rat small intestine. In the Ussing chamber,
exposure to a hypotonic medium caused a decrease in short-circuit current (I
sc) and potential difference (V
ms) in the jejunum, whereas the ileum responded with an increase in I
sc and V
ms. The transition from one pattern to the other was located about in the middle of the small intestine. Tissue conductance
decreased in both segments, probably due to a reduction of paracellular shunt conductance induced by the cell swelling. Voltage
scanning experiments revealed that the observed decrease in total tissue conductance in the ileum was caused solely by a decrease
in local conductance in the villus region while the crypt conductance did not change, suggesting that the decrease in paracellular
conductance of the crypts is compensated by an increase in cellular conductance. The response in both segments was dependent
on the presence of Cl− and was blocked by the Cl− channel blocker 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB). It was not affected by the neurotoxin tetrodotoxin. In the
jejunum the swelling-induced decrease in I
sc was reduced in the presence of the cyclooxygenase inhibitor, indomethacin, or the lipoxygenase inhibitor, nordihydroguaiaretic
acid. In the ileum the Cl− secretion induced by hypotonicity was blocked by the K+ channel blocker quinine and was reversed into a decrease in I
sc when serosal Ca2+ was zero. We conclude that the observed volume regulatory changes are initiated in the jejunum by an eicosanoid-mediated
opening of basolateral Cl− channels and in the ileum by a Ca2+-mediated opening of K+ channels which enhances apical Cl− efflux.
Received: 27 June 1995/Received after revision: 8 December 1995/Accepted: 28 December 1995 相似文献