Cheng Yan-Ping, Wang Yi-He, Cheng Li-Ping, He Rui-Rong
Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China.
Acta Pharmacol Sin. 2003 Aug;24(8):826-30.
To study the electrophysiologic effects of capsaicin on isolated pacemaker cells in sinoatrial (SA) nodes of rabbits and its possible action mechanism(s).
Parameters of action potential (AP) in SA node were recorded using intracellular microelectrode technique.
By perfusion with capsaicin (10 micromol/L), the amplitude of action potential (APA) and maximal rate of depolarization (Vmax) were decreased from (55+/-4) mV to (49+/-4) mV (P<0.05) and from (2.4+/-0.5) V/s to (1.7+/-0.2) V/s (P<0.05). The velocity of diastolic (phase 4) depolarization (VDD) and rate of pacemaker firing (RPF) were decreased from (91+/-34) mV/s to (70+/-30) mV/s (P<0.01) and from (186+/-14) beat/min to (162+/-10) beat/min (P<0.01). The absolute value of maximal diastolic potential (MDP) was decreased from (49+/-3) mV to (44+/-2) mV (P<0.01). However, the duration of 90 % repolarization of action potential (APD90) was prolonged from (149+/-21) ms to (167+/-27) ms (P<0.01). Pretreatment with ruthenium red (RR, 10 micromol/L), a vanilloid receptor (VR1) blocker, did not affect the effects of capsaicin on SA node cells. Both elevation of calcium concentration (5 mmol/L) in superfusate and application of L-type Ca2+ channel agonist Bay-K-8644 (0.5 micromol/L) antagonized the effects of capsaicin on pacemaker cells. Beta-adrenergic agonist isoproterenol (Iso, 20 nmol/L) inhibited the capsaicin-induced prolongation of repolarization and decrease of MDP.
Capsaicin exerted a negative chronotropic action and induced a delayed repolarization of pacemaker cells in SA nodes of rabbits. These effects were likely due to reduction in calcium influx and/or potassium efflux, but were not mediated by VR1.
研究辣椒素对兔窦房结孤立起搏细胞的电生理效应及其可能的作用机制。
采用细胞内微电极技术记录窦房结动作电位（AP）参数。
用辣椒素（10微摩尔/升）灌注后，动作电位幅度（APA）和最大去极化速率（Vmax）分别从（55±4）毫伏降至（49±4）毫伏（P<0.05），从（2.4±0.5）伏/秒降至（1.7±0.2）伏/秒（P<0.05）。舒张期（4期）去极化速度（VDD）和起搏发放频率（RPF）分别从（91±34）毫伏/秒降至（70±30）毫伏/秒（P<0.01），从（186±14）次/分钟降至（162±10）次/分钟（P<0.01）。最大舒张电位（MDP）绝对值从（49±3）毫伏降至（44±2）毫伏（P<0.01）。然而，动作电位90%复极化持续时间（APD90）从（149±21）毫秒延长至（167±27）毫秒（P<0.01）。用香草酸受体（VR1）阻断剂钌红（RR，10微摩尔/升）预处理不影响辣椒素对窦房结细胞的作用。灌流液中钙浓度升高（5毫摩尔/升）和应用L型钙通道激动剂Bay-K-8644（0.5微摩尔/升）均拮抗辣椒素对起搏细胞的作用。β-肾上腺素能激动剂异丙肾上腺素（Iso，20纳摩尔/升）抑制辣椒素诱导的复极化延长和MDP降低。
辣椒素对兔窦房结起搏细胞具有负性变时作用并诱导延迟复极化。这些效应可能是由于钙内流减少和/或钾外流减少所致，但不是由VR1介导的。
