Palmitoyl carnitine modifies sodium currents and induces transient inward current in ventricular myocytes.
Palmitoyl carnitine modifies sodium currents and induces transient inward current in ventricular myocytes.
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棕榈酰肉碱改变钠电流并在心室肌细胞中诱导瞬时内向电流。
DOI：
10.1152/ajpheart.1994.266.3.h1034
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发表时间：
1994
期刊：
影响因子：
--
通讯作者：
Corr,PB
中科院分区：
文献类型：
--
作者：
Wu,J;Corr,PB
长链酰基肉碱在体内缺血心肌2分钟内增加，并在体外诱导延迟后去极化（DADs）和膜电位的复杂振荡。本研究采用全细胞电压钳法对分离的兔心室细胞中这些电生理改变的离子电流进行了评估。棕榈酰肉碱（10微米，持续6-10分钟）在Ca2+和K+通道被阻断的情况下引发瞬时内向电流（Iti）。棕榈酰肉碱的作用在洗脱后是可逆的（n = 6）。它的振幅取决于前一个去极化步骤的振幅。棕榈酰肉碱（10微米，持续bbb2min）也诱导另一个向内电流，该电流在-120和-20 mV之间自发激活，具有线性电流-电压关系（1.0 +/- 0.1 nA, -80 mV）。通过用四乙基氯化铵取代细胞外Na+，该电流被消除，表明Na+是电荷载体。该电流失活缓慢（gamma = 885.9 +/- 89.1 ms, n = 12）或不完全，表明出现了缓慢失活的Na+内向电流[INa(s)]。棕榈酰肉碱总是在Iti出现之前诱导INa(s)。胞内乙二醇-双（β -氨基乙醚）-N，N，N‘，N’-四乙酸（10 mM）可消除Iti，但不抑制INa(s) (N = 4)，表明INa(s)未被胞内Ca2+ (Cai2+)激活。河豚毒素（10 μ m）也降低了INa的振幅(s)。因此，棕榈酰肉碱诱导INa(s)，这可能导致Na+内流增加，从而通过Na(+)-Ca2+交换引起Cai2+增加，并导致Iti、DADs和触发活性的发展。
Long-chain acylcarnitines increase within 2 min in ischemic myocardium in vivo and induce delayed afterdepolarizations (DADs) and complex oscillations of membrane potential in vitro. This study was performed to assess the ionic currents underlying these electrophysiological alterations in isolated rabbit ventricular cells using whole cell voltage-clamp procedures. Palmitoyl carnitine (10 microM, for 6-10 min) elicited a transient inward current (Iti) in the presence of blockade of Ca2+ and K+ channels. The effect of palmitoyl carnitine was reversible after washout (n = 6). The amplitude of Iti was dependent on the amplitude of the preceding depolarization step. Palmitoyl carnitine (10 microM, for > 2 min) also induced another inward current, which was activated spontaneously at potentials between -120 and -20 mV with a linear current-voltage relationship (1.0 +/- 0.1 nA at -80 mV). This current was abolished by replacing extracellular Na+ with tetraethylammonium chloride, indicating that Na+ was the charge carrier. Inactivation of this current was slow (gamma = 885.9 +/- 89.1 ms, n = 12) or incomplete, indicating the appearance of a slow-inactivating Na+ inward current [INa(s)]. Palmitoyl carnitine always induced INa(s) before the appearance of Iti. Intracellular ethylene glycol-bis(beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid (10 mM) abolished Iti but did not suppress INa(s) (n = 4), indicating that INa(s) was not activated by intracellular Ca2+ (Cai2+). Tetrodotoxin (10 microM) also decreased the amplitude of INa(s). Thus palmitoyl carnitine induces INa(s), which likely leads to an increase in Na+ influx, thereby eliciting an increase in Cai2+ via the Na(+)-Ca2+ exchanger and leading to the development of Iti, DADs, and triggered activity.