Voltage-gated K+ channels are the primary regulators of resting membrane potential and intracellular calcium in rat pulmonary arterial smooth muscle cells.
The membrane potential (Em) of pulmonary arterial smooth muscle cells (PASMCs) regulates pulmonary arterial tone by controlling voltage-gated Ca2+ channel activity, which is a major contributor to Ca2+i. The resting membrane is mainly permeable to K+; thus, the resting Em is controlled by K+ permeability through sarcolemmal K+ channels. At least three K+ currents, voltage-gated K+ (KV) currents, Ca(2+)-activated K+ (KCa) currents, and ATP-sensitive (KATP) currents, have been identified in PASMCs. In this study, both patch-clamp and quantitative fluorescent microscopy techniques were used to determine which kind(s) of K+ channels (KV, KCa, and/or KATP) is responsible for controlling Em and Ca2+i under resting conditions in rat PASMCs. When the bath solution contained 1.8 mmol/L Ca2+ and the pipette solution included 0.1 mmol/L EGTA, depolarizations (-40 to +80 mV) elicited both KCa and KV currents. Removal of extracellular Ca2+ and increase of intracellular EGTA concentration (to 10 mmol/L) eliminated the Ca2+ influx-dependent KCa current. 4-Aminopyridine (4-AP, 5 to 10 mmol/L) but not charybdotoxin (ChTX, 10 to 20 nmol/L) significantly reduced KV current under these conditions. In current-clamp experiments, 4-AP decreased Em (depolarization) and induced Ca(2+)-dependent action potentials; this depolarization increased Ca2+i in intact PASMCs. Neither ChTX nor the specific blocker of KATP channels, glibenclamide (2 to 10 mumol/L), caused membrane depolarization and the increase in Ca2+i. However, pretreatment of PASMCs with ChTX enhanced the 4-AP-induced increase in Ca2+i.(ABSTRACT TRUNCATED AT 250 WORDS)
Xiao-Jian Yuan (Tue,) studied this question.