Format

Send to

Choose Destination
Circ Res. 1995 Aug;77(2):370-8.

Voltage-gated K+ currents regulate resting membrane potential and [Ca2+]i in pulmonary arterial myocytes.

Author information

1
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.

Abstract

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).

PMID:
7542182
DOI:
10.1161/01.res.77.2.370
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Atypon
Loading ...
Support Center