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耳蜗支持细胞中缝隙连接的电压门控:非同源通道的证据。

Voltage gating of gap junctions in cochlear supporting cells: evidence for nonhomotypic channels.

作者信息

Zhao H B, Santos-Sacchi J

机构信息

Sections of Otolaryngology and Neurobiology, Yale University School of Medicine, New Haven, CT 06511, USA.

出版信息

J Membr Biol. 2000 May 1;175(1):17-24. doi: 10.1007/s002320001051.

DOI:10.1007/s002320001051
PMID:10811964
Abstract

The organ of Corti has been found to have multiple gap junction subunits, connexins, which are localized solely in nonsensory supporting cells. Connexin mutations can induce sensorineural deafness. However, the characteristics and functions of inner ear gap junctions are not well known. In the present study, the voltage-dependence of gap junctional conductance (G(j)) in cochlear supporting cells was examined by the double voltage clamp technique. Multiple types of asymmetric voltage dependencies were found for both nonjunctional membrane voltage (V(m)) and transjunctional (V(j)) voltage. Responses for each type of voltage dependence were categorized into four groups. The first two groups showed rectification that was polarity dependent. The third group exhibited rectification with either voltage polarity, i.e., these cells possessed a bell-shaped G(j)-V(j) or G(j)-V(m) function. The rectification due to V(j) had fast and slow components. On the other hand, V(m)-dependent gating was fast (<5 msec), but stable. Finally, a group was found that evidenced no voltage dependence, although the absence of V(j) dependence did not preclude V(m) dependence and vice versa. In fact, for all groups V(j) sensitivity could be independent of V(m) sensitivity. The data show that most gap junctional channels in the inner ear have asymmetric voltage gating, which is indicative of heterogeneous coupling and may result from heterotypic channels or possibly heteromeric configurations. This heterogeneous coupling implies that single connexin gene mutations may affect the normal physiological function of gap junctions that are not limited to homotypic configurations.

摘要

已发现柯蒂氏器有多种间隙连接亚基,即连接蛋白,它们仅定位于非感觉性支持细胞中。连接蛋白突变可导致感音神经性耳聋。然而,内耳间隙连接的特性和功能尚不清楚。在本研究中,采用双电压钳技术检测了耳蜗支持细胞中间隙连接电导(G(j))的电压依赖性。对于非连接膜电压(V(m))和跨连接(V(j))电压,发现了多种类型的不对称电压依赖性。每种电压依赖性的反应分为四组。前两组表现出与极性相关的整流。第三组在任何一种电压极性下均表现出整流,即这些细胞具有钟形的G(j)-V(j)或G(j)-V(m)函数。由V(j)引起的整流有快速和慢速成分。另一方面,V(m)依赖性门控快速(<5毫秒)但稳定。最后,发现一组细胞没有电压依赖性,尽管不存在V(j)依赖性并不排除V(m)依赖性,反之亦然。事实上,对于所有组,V(j)敏感性可能独立于V(m)敏感性。数据表明,内耳中的大多数间隙连接通道具有不对称电压门控,这表明存在异质偶联,可能是由异型通道或可能的异聚体构型导致的。这种异质偶联意味着单个连接蛋白基因突变可能影响间隙连接的正常生理功能,而不仅限于同型构型。

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