MODULATION OF VOLTAGE-DEPENDENT K-MUSCLE CELLS OF THE RABBIT( CHANNELBY REDOX POTENTIAL IN PULMONARY AND EAR ARTERIAL SMOOTH)

It has been suggested that hypoxic pulmonary vasoconstriction (HPV) re sults from the depolarization that is induced by the suppression of K current in pulmonary arterial smooth muscle cells (PASMC). We tested the hypothesis that the effect of the cellular redox potential on volt age-sensitive K+ (Kv) current is involved in HPV as a primary sensing mechanism. Kv current in PASMC and ear arterial smooth muscle cells (E ASMC) of the rabbit was recorded using the whole-cell patch-clamp tech nique, and the effect of redox agents [dithiothreitol, DTT and 2,2'-di thio-bis(5-nitropyridine), DTBNP] was tested. Kv current was decreased by DTT, but increased by DTBNP. DTT accelerated the inactivation kine tics, but did not affect steady-state activation and inactivation, whe reas DTBNP accelerated activation kinetics. Kv current has a non-inact ivating window in the range of from -40 mV to +10 mV. The resting memb rane potential measured using the nysratin-perforated-patch method, ho wever, lay between -50 mV and -30 mV and was not depolarized by 5 mM 4 -aminopyridine. The membrane-impermeable oxidizing agent DTNB has no e ffect on Kv current, suggesting that redox modulation sites are intrac ellular sulphydryl groups. In EASMC, Kv current was decreased by DTT, but increased by DTBNP, indicating that the redox-potential-induced mo dulation of Kv current in EASMC and in PASMC is the same. It is theref ore concluded that Kv current is modulated by the cellular redox poten tial, but that this modulation is not involved in HPV as a primary sen sing mechanism.