| 15127573 |
Fan ZW, Zhang ZX, Xu YJ: [Inhibition of voltage-gated K+ current in rat intrapulmonary arterial smooth muscle cells by endothelin-1]. Yao Xue Xue Bao. 2004 Jan;39(1):9-12.
AIM: To investigate the role of endothelin-1 (ET-1) in the physiological and pathophysiological regulating mechanisms of voltage-gated K+ current (IKV) inhibition in rat intrapulmonary arterial smooth muscle cells (PASMCs). METHODS: Single PASMCs were obtained with acute enzyme (collagnase plus papain) dispersing method. Using whole cell patch-clamp technique in freshly isolated rat PASMCs, the effect of ET-1 on voltage-gated K+ current was recorded. RESULTS: ET-1 (1 x 10 (-9) mol.L-1) and the voltage-dependent K+ (KV)-channel antagonist 4-aminopyridine (4AP), but not the Ca (2+)-activated K (+)-channel antagonist tetraethylammonium (TEA), caused membrane depolarization. The effect of ET-1 on membrane potential persisted in cells in which intracellular Ca2+ was buffered with 1,2-bis (2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA). ET-1 (1 x 10 (-9) mol.L-1) caused a significant reversible inhibition of KV current, which began 4.0 s after application of ET-1, was much earlier than the effect of membrane depolarization of PASMCs (15s). ET-1 (1 x 10 (-10) to 1 x 10 (-7) mol.L-1) caused a concentration-dependent inhibition of K+ current ( mV, from 136 to 40 pA/pF). The percent inhibition was 71% at 1 x 10 (-7) mol.L-1 (n = 6). The effect of ET-1 (1 x 10 (-9) mol.L-1) on K+ current was weaker under conditions free of Ca2+ than containing Ca2+. At a test potential of mV, free of Ca2+ conditions reduced the maximum inhibitory effect of ET-1 from 71% to 50%. CONCLUSION: ET-1 modulated pulmonary vascular reactivity by depolarizing membrane potential and inhibiting the K+ current of PASMCs. The effect of ET-1 on PASMCs membrane potential and the inhibition of K+ current were independent of Ca2+, but the inhibition of K+ current was much greater under conditions containing Ca2+ than free of Ca2+. |
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