Cholinergic agonists suppress a potassium current in freshly dissociated smooth muscle cells of the toad.
Cholinergic agonists suppress a potassium current in freshly dissociated smooth muscle cells of the toad.
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胆碱能激动剂抑制蟾蜍新鲜分离的平滑肌细胞中的钾电流。
DOI：
10.1113/jphysiol.1985.sp015837
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
WalshJr,JV
中科院分区：
文献类型：
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作者：
Sims,SM;Singer,JJ;WalshJr,JV
应用单微电极电压钳和电流钳技术研究了蟾蜍胃平滑肌细胞胆碱能反应。乙酰胆碱（ACh）或毒蕈碱引起膜去极化，有时引起动作电位和收缩。激动剂诱导的去极化是由于电压依赖性K+电导的抑制，这是基于以下观察结果得出的结论。去极化伴随着明显的膜电导下降，被视为响应于恒定电流脉冲的电压偏转的大小增加。在电压钳下确认电导降低，其中在胆碱能激动剂的存在下，响应于恒定电压跳变的电流偏转较小。毒蕈碱诱导的净内向电流的电位正的K+平衡电位（EK），和净外向电流的电位负的EK。在外部K+浓度（[K+]o）范围为20至90 mM的实验中，[K+]o每升高10倍，反转电位正移58 mV，与K+电流的预期一致。稳态电流-电压关系显示，在更正的电位下，毒蕈碱抑制的K+电流大于仅考虑驱动力时的预期。因此，胆碱能激动剂抑制的潜在电导是电压依赖性的，在比约-70 mV更负的电位下几乎完全失活，并且在去极化时表现出S形激活曲线。这种电压依赖性K+电导的失活导致响应于来自去极化保持电位的超极化电压命令而发生缓慢电流弛豫。在[K+]o范围为3至30 mM的实验中，这些电流弛豫在EK附近的电位处反转方向，并且[K+]o每升高10倍，反转电位正移52 mV，表明K离子携带大部分电荷。乙酰胆碱、毒蕈碱和氧化震颤素可抑制超极化电压指令引起的电流弛豫。在含有Mn 2+的标称无Ca 2+溶液中，毒蕈碱的作用持续存在。Ba 2+模拟毒蕈碱激动剂的作用。因此，分离的平滑肌细胞表现出类似于交感神经元和其他神经元的M-电流的K+电流，其被胆碱能激动剂可逆地抑制。胆碱能K+电导降低的存在是令人感兴趣的，因为它以前没有被证明在平滑肌。
Single micro‐electrode voltage‐clamp and current‐clamp techniques were used to study cholinergic responses in single freshly isolated gastric smooth muscle cells from the toad Bufo marinus. Acetylcholine (ACh) or muscarine caused membrane depolarization, which sometimes gave rise to action potentials and contractions. The agonist‐induced depolarization is due to the suppression of a voltage‐dependent K+ conductance, a conclusion based on the following observations. Depolarization was accompanied by an apparent membrane conductance decrease, seen as the increased size of voltage deflexions in response to constant current pulses. The conductance decrease was confirmed under voltage clamp, where current deflexions in response to constant voltage jumps were smaller in the presence of cholinergic agonists. Muscarine induced net inward currents at potentials positive to the K+ equilibrium potential (EK), and net outward currents at potentials negative to EK. In experiments where external K+ concentration ([K+]o) ranged from 20 to 90 mM the reversal potentials shifted 58 mV positive per tenfold elevation of [K+]o, as expected for a K+ current. The steady‐state current‐voltage relationship revealed that the K+ current inhibited by muscarine was larger at more positive potentials than expected from driving force considerations alone. Therefore, the underlying conductance suppressed by cholinergic agonists was voltage dependent, with almost complete deactivation at potentials more negative than approximately ‐70 mV and exhibiting a sigmoidal activation curve upon depolarization. The deactivation of this voltage‐dependent K+ conductance caused slow current relaxations to occur in response to hyperpolarizing voltage commands from depolarized holding potentials. In experiments where [K+]o ranged from 3 to 30 mM, these current relaxations reversed direction at potentials near EK and the reversal potential shifted 52 mV positive per tenfold elevation of [K+]o, indicating that K ions carry most of the charge. The current relaxations that occurred in response to hyperpolarizing voltage commands were suppressed by ACh, muscarine and oxotremorine. The effects of muscarine persisted in nominally Ca2+‐free solutions containing Mn2+. Ba2+ mimicked the effects of muscarinic agonists. Thus, isolated smooth muscle cells exhibit a K+ current resembling the M‐current of sympathetic and other neurones, which is reversibly suppressed by cholinergic agonists. The existence of a cholinergic K+ conductance decrease is of interest because it has not previously been demonstrated in smooth muscle.