Sunami A, Sasano T, Matsunaga A, Fan Z, Swanobori T, Hiraoka M
Department of Cardiovascular Diseases, Tokyo Medical and Dental University, Japan.
Am J Physiol. 1993 Feb;264(2 Pt 2):H454-63. doi: 10.1152/ajpheart.1993.264.2.H454.
Modification of single Na+ channels by the alkaloid neurotoxin veratridine was investigated in guinea pig ventricular myocytes using the cell-attached configuration of the patch-clamp technique. Pipette application of veratridine (50 microM) induced long-lasting openings with two different single-channel conductances of 7.6 and 3.0 pS, in addition to normal type of short openings with a single-channel conductance of 16 pS. The veratridine-modified high- and low-conductance channels appeared commonly, and they could coexist with the normal one in the same patch. The open-time distributions for the high- and low-conductance channels could be fitted by a single exponential. The mean open time for the high- and low-conductance events ranged between 19.1 ms at -120 mV and 86.0 ms at -10 mV and between 4.5 ms at -120 mV and 16.2 ms at -10 mV, respectively. The closed-time distributions for the two conductance channels consisted of at least two components, and their values and voltage dependence were similar. External Ca2+ block resulted in an apparent reduction of unitary current amplitudes with a similar voltage dependence and affinity for Ca2+ in the high- and low-conductance channels. However, the low-conductance channel was more resistant to tetrodotoxin than the high one. The probability of simultaneous occurrence of the high and low events was equal to the product of the probabilities of occurrence of the high event times that of the low event. Furthermore, we observed modified channel openings after a normal opening for the two conductance channels and a modified one turning into a normal one for the high-conductance channel. It is concluded that veratridine induces the two different types of modified Na+ channels in cardiac myocytes and these are correlated with normal openings.
采用膜片钳技术的细胞贴附式记录模式，研究了生物碱神经毒素藜芦定对豚鼠心室肌细胞单个钠离子通道的修饰作用。向膜片钳微管内施加藜芦定（50微摩尔），除了诱导出正常类型的单通道电导为16皮西门子的短开放外，还诱导出了两种不同单通道电导分别为7.6和3.0皮西门子的持久开放。藜芦定修饰的高电导和低电导通道普遍出现，它们可与正常通道在同一膜片中共存。高电导和低电导通道的开放时间分布可用单一指数函数拟合。高电导和低电导事件的平均开放时间分别在-120毫伏时为19.1毫秒至-10毫伏时为86.0毫秒之间，以及-120毫伏时为4.5毫秒至-10毫伏时为16.2毫秒之间。两种电导通道的关闭时间分布至少由两个成分组成，其数值和电压依赖性相似。细胞外钙离子阻断导致高电导和低电导通道的单位电流幅度明显降低，且对钙离子具有相似的电压依赖性和亲和力。然而，低电导通道比高电导通道对河豚毒素更具抗性。高、低事件同时发生的概率等于高事件发生概率与低事件发生概率的乘积。此外，我们还观察到两种电导通道在正常开放后出现修饰通道开放，以及高电导通道的修饰通道转变为正常通道的情况。结论是藜芦定可诱导心肌细胞中两种不同类型的修饰钠离子通道，且这些通道与正常开放相关。
