AIMTo investigate the effect of endothelin-1 (ET-1) on voltage-gated K+ current in the pulmonary artery smooth muscle cells (PASMCs) of chronic hypoxic rats.

METHODSTwelve male Wistar rats matched with age and body weight were randomly divided into control and chronic hypoxic groups. Single PASMCs were obtained with acute enzyme (collagnase plus papain) dispersing method. Using the whole cell patch clamp technique in freshly isolated PASMCs from normoxic and hypoxic rats, the effects of ET-1 on voltage-gated K+ current were recorded.

RESULTSThe resting membrane potential (Em) in PASMCs from chronic hypoxic rats was significantly depolarized to (-32.6 +/- 1.3) mV compared with (-42.1 +/- 2.8) mV in PASMCs from normoxic rats (P < 0.01, n = 20). In chronic hypoxic rats, the IKv was smaller than that in normotensive rats [+50 mV, the peak current density of control group reduced from (136 +/- 24) pA/pF to (98 +/- 12) pA/pF, percent inhibition was (28.4 +/- 2.4)%, P < 0.01, n = 6]. Application of ET-1 (1 x 10(-8) mol x L(-1)) also depolarized PASMCs of chronic hypoxic rats from (-32.6 +/- 1.3) mV to (-21.5 +/- 1.7) mV (P < 0.05, n = 20) compared with the ET-1 induced depolarization from (-42.1 +/- 2.8) mV to (-22.6 +/- 1.4) mV (P < 0.05, n = 20). The change in membrane potential induced by ET-1 was not significantly different between PASMCs from normoxic and hypoxic rats. ET-1 (1 x 10(-10) to 1 x 10(-7) mol x L(-1)) caused concentration-dependent inhibition of K+ current in PASMCs both from normoxic and hypoxic rats. At higher concentration (1 x 10(-8) - 1 x 10(-7) mol x L(-1)), the effect of ET-1 on K+ current in PASMCs from hypoxic rats was greater than that of normoxic rats [+50 mV, the peak current density of control group reduced from (136 +/- 24) pA/pF to (40 +/- 10) pA/pF, percent inhibition was (71 +/- 7)%, that of hypoxic group was (98 +/- 6) pA/pF to (16 +/- 3) pA/pF, percent inhibition was (85 +/- 10)% at 1 x 10(-7) mol x L(-2), n = 6, P < 0.01].

CONCLUSIONChronic hypoxia did not change the effect of ET-1 on the passive electrical properties of PASMCs. In both normotensive and chronic hypoxic hypertensive PASMCs, exogenous ET-1 could cause concentration-dependent inhibition of voltage-gated K+ current, and the inhibition of K+ current in PASMCs from chronic hypoxic rats was greater than that from normoxic rats at higher concentration (1 x 10(-8) - 1 x 10(-7) mol x L(-1)). Chronic hypoxia might alter the sensitivity of PASMCs to ET-1, perhaps PASMCs exposed to chronic hypoxia were more susceptible to ET-1 mediated IKv inhibition.