The newborn rabbit sino-atrial node expresses a neuronal type I-like Na+ channel
The newborn rabbit sino-atrial node expresses a neuronal type I-like Na+ channel
复制标题
DOI：
10.1113/jphysiol.1997.sp021889
复制
发表时间：
1997-02-01
影响因子：
5.5
通讯作者：
Robinson, RB
中科院分区：
文献类型：
--
作者：
Baruscotti, M;Westenbroek, R;Robinson, RB
1.新近发现新生兔窦房结（SAN）肌细胞表达河豚毒素（TTX）敏感性钠电流。我们现在报告说，剂量-反应关系表明，这种SAN Na+通道具有异常高的TTX敏感性，具有半数最大抑制（26 +/- 5 nM），这在神经元中比在心脏组织中更典型。另外的表征使用μ-芋螺毒素GIIIA和Cd 2+作为骨骼和心脏同种型的相对选择性阻断剂。μ-芋螺毒素GIIIA对从SAN肌细胞记录的电流没有影响，但是对于神经元同种型，Cd 2+敏感性出乎意料地高（半最大抑制= 185 +/- 8 μ M）。灭活时间常数的分析未显示多个灭活过程的证据，数据与单个相对快速的指数拟合良好（0 mV时灭活时间常数= 0.58 +/- 0.03 ms）。使用反义cDNA探针原位杂交来测试神经元I型、II型和III型Na+通道亚型的表达。新生儿SAN组织中的心肌细胞表现出明显的杂交I型，但不是II型或III型探针。三种探针在成人SAN组织中均未观察到杂交.它的结论是，新生儿SAN表达神经元I型样Na+通道亚型，这可能是占TTX和Cd 2+的高敏感性的不寻常的特性。
1. Newborn rabbit sino-atrial node (SAN) myocytes were recently found to express a tetrodotoxin (TTX)-sensitive Na+ current. We now report that the dose-response relation indicates that this SAN Na+ channel has unusually high TTX sensitivity, with half-maximal inhibition (26 +/- 5 nM) which is more typical of neuronal than cardiac tissue.2. Additional characterization used mu-conotoxin GIIIA and Cd2+ as relatively selective blockers of the skeletal and cardiac isoforms, respectively. mu-Conotoxin GIIIA had no effect on the current recorded from SAN myocytes, but the Cd2+ sensitivity was unexpectedly high for a neuronal isoform (half-maximal inhibition = 185 +/- 8 mu M).3. Analysis of the time constant of inactivation did not reveal evidence of multiple inactivation processes, with the data well fitted by a single, relatively rapid exponential (inactivation time constant = 0.58 +/- 0.03 ms at 0 mV).4. In situ hybridization with anti-sense cDNA probes was used to test for expression of neuronal type I, II and III Na+ channel isoforms. Myocardial cells in newborn SAN tissue exhibited clear hybridization to the type I, but not the type II or III probes. No hybridization was observed in adult SAN tissue with any of the three probes.5. It is concluded that the newborn SAN expresses a neuronal type I-like Na+ channel isoform, and that this probably accounts for the unusual characteristic of high sensitivity to both TTX and Cd2+.