Hypoxia reduces potassium currents in cultured rat pulmonary but not mesenteric arterial myocytes

Abstract

To explore possible mechanisms underlying hypoxia-induced pulmonary vasoconstriction, the effect of hypoxia on outward K+ current (Iout) was evaluated in primary cultured rat pulmonary (PA) and mesenteric (MA) arterial smooth muscle cells using the whole cell patch-clamp technique. When the cells were bathed in standard physiological salt solution and the patch pipettes contained Ca(2+)-free media with 10 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), virtually all of the Iout, including both the rapidly inactivating component (Irt) and the steady-state (noninactivating) component (Iss), was mediated by voltage-gated K+ channels. Reduction of O2 tension in the bath solution from 155 Torr to < 74 Torr with sodium dithionite reversibly inhibited both Irt and Iss in PA myocytes, but not in MA myocytes. The hypoxia-sensitive Iss was activated at about -50 mV; thus, some of the channels responsible for this current may be open at the resting membrane potential (-40 +/- 1 mV) of PA cells used in this study. Hypoxia also significantly depolarized PA cells bathed in PSS (1.8 mM Ca2+) from -40.7 +/- 1.3 to -24.0 +/- 2.4 mV, and PA cells bathed in Ca(2+)-free PSS (0.1 mM EGTA) from -38.4 +/- 1.3 to -26.1 +/- 3.9 mV. The hypoxia-induced inhibition of Iout in PA cells was accompanied by an apparent increase in inward Ca2+ current.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between membrane potential, delayed rectifier K+ currents and hypoxia in rat pulmonary arterial myocytes

“…However, no previous isolated cell studies have shown that a 'priming' depolarization is a prerequisite for subsequent depolarization in response to hypoxia. In some studies (for example, Yuan et al 1993Yuan et al , 1994) the membrane potential in normoxic conditions was more depolarized than that observed in our study, thereby (perhaps) rendering cells sensitive to hypoxia. This difference, and the possibility that cells from different species may respond to hypoxia in a subtly different manner, could explain the discrepancy between our results and those of others.…”

Patho-, physiological roles of voltage-dependent K+ channels in pulmonary arterial smooth muscle cells

“…This effects of accompanied by an enhancement of the inward Ca 2+ current in the pulmonary artery, an effect not observed in MASMCs (Yuan et al, 1990;Yuan et al, 1993). Delayed rectifier currents that are sensitive to 4-AP are deemed to be important determinants of resting membrane potential (Em) and critical in the initiation of HPV (Post et al, 1992;Archer et al, 1998).…”

“…Post and colleagues were the first to identify K + channel inhibition as a key event in the mechanisms of HPV via their role in membrane depolarization and subsequent opening of voltage-gated Ca 2+ channels and the promotion Ca 2+ entry (Post et al, 1992). Indeed, decreased Kv channel currents have been observed in response to acute hypoxia in both rat and mouse PASMCs (Archer et al, 1993(Archer et al, , 2001Yuan et al, 1993;Turner and Kozlowski, 1997;Platoshyn et al, 2006). Also note that Smirnov et al (1994) showed that chronic hypoxia (PO2 30-35 mmHg) causes a marked (40-50%) reduction in Kv currents amplitude, and chronically hypoxic animals have a significantly more positive (-43.5 ± 2 mV) resting membrane potential in PASMCs (Smirnov et al, 1994).…”

International Hypoxia Symposium (13th) for the Publishing of the Conference Proceedings for 2003 Conference

“…The importance of redox processes in HIF-1 response has come to light in recent years with reports revealing that ROS may trigger HIF-la fimction (16,31,52,53,67,94,125,154). However, the role of the mitochondrial respiratory chain -one of the most well known sources of ROS -is still controversial (18,19,138,149).…”

“…Also, it is possible that apoptosis in the endothelial cells is different than the apoptosis in the smooth muscle cells in the PA media. Nevertheless, Yuan et al recently showed that NO might induce PASMC apoptosis by activating Kv and KCa channels as well as depolarizing mitochondrial membrane potential (AYm) (149). The opening of sarcolemmal K* channels would cause efflux of K* and therefore osmotic cell shrinkage, which is known to initiate apoptosis; A'I'm depolarization has also been implicated in the initiation of apoptosis (29).…”