Castle N A
Department of Anesthesia Research Laboratories, Brigham and Women's Hospital, Boston, MA 02115.
Cardiovasc Res. 1992 Nov;26(11):1137-44. doi: 10.1093/cvr/26.11.1137.
Capsaicin is a pungent irritant present in peppers of the Capsicum family. Its major target of action is believed to be sensory neurones. Capsaicin has also been shown to prolong cardiac action potential in atrial muscle, perhaps by local release of calcitonin gene related peptide which in turn enhances inward calcium currents. However, capsaicin has been shown to inhibit K+ current in neurones. Since such an action could contribute to action potential prolonging activity of capsaicin in heart, the aim of the study was to examine the effects of capsaicin on cardiac K+ currents.
Ionic currents and action potentials were examined in isolated adult rat ventricular myocytes using the whole cell variant of the patch clamp technique at 25 degrees C.
Capsaicin (10 microM) increased the action potential duration (APD50) from 45 ms to 166 ms. This effect was associated with an inhibition of three distinct K+ currents. The decreasing rank order of potency was: transient outward K+ current (ITO, IC50 = 6.4 microM), a voltage dependent non-inactivating outward current (IK, IC = 11.5 microM), and the inward rectifier K+ current (IK1, IC50 = 46.9 microM). Capsaicin induced block of ITO was characterised by a decrease in the peak current amplitude and an increase in the rate of inactivation. The inactivation of ITO in the absence of capsaicin was well described by a single exponential [tau = 77 (SEM 2) ms at +40 mV, n = 10]. However, in the presence of 10 microM capsaicin inactivation was best described by the sum of two exponentials [tau FAST = 4.4(0.5) ms; tau SLOW = 92.4(3.0) ms, n = 10] with the fast component contributing 46(2)% of the total decay. A small but consistent hyperpolarising shift (approximately 3 mV) in the steady state voltage dependence of inactivation of ITO was induced by 10 microM capsaicin. Capsaicin had no effect on the rate of ITO recovery from inactivation (tau = 49 ms and 48 ms for control and drug respectively). The capsaicin analogue, resiniferatoxin, which as an irritant is up to 10(4)-fold more potent than capsaicin, had no effect on any of the K+ currents when present at concentrations of up to 10 microM. In contrast another capsaicin analogue, zingerone (30 microM) blocked ITO by 52(12)% and IK by 35%.
Capsaicin produces a prolongation of the rat ventricular action potential, an effect which is associated with inhibition of potassium currents.
辣椒素是辣椒属植物辣椒中存在的一种刺激性物质。其主要作用靶点被认为是感觉神经元。辣椒素还被证明可延长心房肌的心脏动作电位，这可能是通过局部释放降钙素基因相关肽实现的，而降钙素基因相关肽又会增强内向钙电流。然而，辣椒素已被证明可抑制神经元中的钾电流。由于这种作用可能有助于辣椒素在心脏中延长动作电位的活性，本研究的目的是研究辣椒素对心脏钾电流的影响。
在25℃下，使用膜片钳技术的全细胞变体，在分离的成年大鼠心室肌细胞中检测离子电流和动作电位。
辣椒素（10微摩尔）使动作电位持续时间（APD50）从45毫秒增加到166毫秒。这种作用与三种不同钾电流的抑制有关。效力降低的顺序为：瞬时外向钾电流（ITO，IC50 = 6.4微摩尔）＞电压依赖性非失活性外向电流（IK，IC = 11.5微摩尔）＞内向整流钾电流（IK1，IC50 = 46.9微摩尔）。辣椒素诱导的ITO阻断的特征是峰值电流幅度降低和失活速率增加。在不存在辣椒素的情况下，ITO的失活可用单一指数很好地描述[在+40毫伏时，τ = 77（标准误2）毫秒，n = 10]。然而，在存在10微摩尔辣椒素的情况下，失活最好用两个指数的总和来描述[快速τ = 4.4（0.5）毫秒；慢速τ = 92.4（3.0）毫秒，n = 10]，快速成分占总衰减的46（2）%。10微摩尔辣椒素诱导ITO失活的稳态电压依赖性出现小但一致的超极化偏移（约3毫伏）。辣椒素对ITO从失活中恢复的速率没有影响（对照组和药物组的τ分别为49毫秒和48毫秒）。辣椒素类似物树脂毒素作为一种刺激性物质，其效力比辣椒素高10^4倍，当浓度高达10微摩尔时，对任何钾电流都没有影响。相比之下，另一种辣椒素类似物姜辣素（30微摩尔）使ITO阻断52（12）%，使IK阻断35%。
辣椒素可使大鼠心室动作电位延长，这种作用与钾电流的抑制有关。
