SELECTIVE BLOCK OF DELAYED RECTIFYING POTASSIUM CURRENT IN THE RABBIT SINOATRIAL NODE BY A NOVEL CLASS-III ANTIARRHYTHMIC AGENT MS-551

被引：5
作者：
SAEKI, T [1 ]
NISHIMURA, M [1 ]
FOLLMER, CH [1 ]
WATANABE, Y [1 ]
机构：
[1] FUJITA HLTH UNIV,SCH MED,INST CARDIOVASC,TOYOAKE,AICHI 47011,JAPAN
来源：
HEART AND VESSELS | 1994年 / 9卷 / 02期
关键词：
MS-551; CLASS III ANTIARRHYTHMIC AGENT; K+ CHANNEL BLOCKER; DELAYED RECTIFYING K+ CURRENT; SINOATRIAL NODE;
D O I：
10.1007/BF01751942
中图分类号：
R5 [内科学];
学科分类号：
1002 ; 100201 ;
摘要：
Electrophysiological actions of MS-551, a novel class III antiarrhythmic agent, were studied using small preparations (0.2 x 0.2 x 0.1mm) of the rabbit sinoatrial (SA) node. MS-551 (0.1-3 mu M) exerted a negative chronotropic action by prolonging the action potential duration and diastolic interval. Automaticity was completely suppressed in 5 of 6 preparations at 1-3 mu M. Voltage clamp experiments using double microelectrode techniques revealed that MS-551 (0.1-10 mu M) blocked the delayed rectifying K+ current (I-K) in a concentration-dependent manner, and the block was almost saturated at > 1 mu M, attaining 60% +/- 10% at 10 mu M (n = 5). The MS-551-sensitive I-K tail (K-d = 0.4 mu M, Hill r = 1.4, n = 5) had fast and slow components of deactivation. MS-551 (1 mu M) reduced the amplitudes of control I-K fast and I-K slow from 20 +/- 4 and 11 +/- 4nA to 8 +/- 3 and 5 +/- 3nA, respectively (P < 0.01, n = 4). Although the fast deactivation time constant at -60mV remained unaltered (127 +/- 12vs 113 +/- 13ms), the slow deactivation time constant was prolonged from 1,117 +/- 130 to 1,555 +/- 407ms by 1 mu M MS-551 (P < 0.05). This agent shifted the steady-state activation curve for I-K from -21 +/- 2 to -26 +/- 4mV and increased the slope factor from 8 +/- 1 to 9 +/- 1mV (P < 0.05, n = 4). The fully-activated IK exhibited prominent inward rectification and was reduced by MS-551. These results suggest that (1) MS-551 prolongs the action potential duration and diastolic interval, and exerts a negative chronotropic action by blocking I-K, (2) MS-551 has a higher affinity for the activated than the resting state K+ channel, and (3) this agent may either preferentially block one type of I-K, Or stabilize a single population of I-K in a subconductance state in the rabbit SA node.
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页码：87 / 95
页数：9
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