TRPC4 currents have properties similar to the pacemaker current in interstitial cells of Cajal.

TRPC4 currents have properties similar to the pacemaker current in interstitial cells of Cajal.
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TRPC4 电流具有与 Cajal 间质细胞中的起搏器电流相似的特性。

DOI:
10.1152/ajpcell.00266.2002
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发表时间:
2002
期刊:
American journal of physiology. Cell physiology
影响因子:
--
通讯作者:
Horowitz,Burton
Horowitz,Burton
中科院分区:
--
文献类型:
--
作者:
Walker,RebeccaL;Koh,SangDon;Sergeant,GerardP;Sanders,KentonM;Horowitz,Burton

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Cajal间质细胞(Interstitial cells of Cajal,ICC)是胃肠道(GI)相位肌中负责电慢波产生和传播的起搏细胞。启动每个慢波的起搏电流来自钙抑制、电压非依赖性、非选择性阳离子通道。ICC中的该通道显示出与非选择性阳离子通道的瞬时受体电位(TRP)家族报告的特性类似的特性,特别是TRPC 3和TRPC 4所见的特性。我们已经在单独分离的ICC中鉴定了TRPC 4的转录物,并从GI肌肉中克隆了TRPC 4的两种选择性剪接形式,TRPC 4 α和TRPC 4 β。TRPC 4 β在羧基末端缺失了一个84个氨基酸的片段。通过N-甲基-D-葡糖胺替代实验和BAPTA透析测定,使用全细胞膜片钳技术表达任一形式导致钙抑制的非选择性阳离子通道。在全细胞水平记录的TRPC 4 β通道的表达具有与ICC的非选择性阳离子电流相似的特征。TRPC 4 β的单通道电导测定为17.5 pS。钙咪达唑鎓对表达TRPC 4 β的细胞的应用导致这些细胞在全细胞和单通道水平上的内向电流显著增加,并且电流对10 μM镧、尼氟灭酸和DIDS的阻断敏感。比较ICC中非选择性阳离子电流的特性和TRPC 4 β的特性,我们得出结论,TRPC 4样电流编码小鼠小肠质膜起搏电流。
Interstitial cells of Cajal (ICC) are the pacemaker cells responsible for the generation and propagation of electrical slow waves in phasic muscles of the gastrointestinal (GI) tract. The pacemaker current that initiates each slow wave derives from a calcium-inhibited, voltage-independent, nonselective cation channel. This channel in ICC displays properties similar to that reported for the transient receptor potential (TRP) family of nonselective cation channels, particularly those seen for TRPC3 and TRPC4. We have identified transcripts for TRPC4 in individually isolated ICC and have cloned the two alternatively spliced forms of TRPC4, TRPC4α and TRPC4β, from GI muscles. TRPC4β is missing an 84-amino acid segment from the carboxy terminus. Expression of either form using the whole cell patch-clamp technique led to calcium-inhibited, nonselective cation channels as determined byN-methyl-d-glucamine replacement experiments and BAPTA dialysis. Expression of TRPC4β channels recorded at the whole cell level had characteristics similar to the nonselective cation current in ICC. The single-channel conductance of TRPC4β was determined to be 17.5 pS. Application of calmidazolium to cells expressing TRPC4β led to a significant increase in the inward current of these cells at both the whole cell and single-channel level, and currents were sensitive to block by 10 μM lanthanum, niflumic acid, and DIDS. Comparison of the properties reported for the nonselective cation current in ICC and those identified here for TRPC4β led us to conclude that a TRPC4-like current encodes the plasmalemmal pacemaker current in murine small intestine.
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