Submitted on March 27, 2008
Revised on May 1, 2008
Accepted on May 3, 2008
Mitochondria Dependent Regulation of Kv Currents in Rat Pulmonary Artery Smooth Muscle Cells
Amy L. Firth, Kathryn H Yuill1, and Sergey V Smirnov1*
1 University of Bath
* To whom correspondence should be addressed. E-mail: s.v.smirnov{at}bath.ac.uk.
Voltage-gated K+ (Kv) channels are important in the regulation of pulmonary vascular function having both physiological and pathophysiological implications. The pulmonary vasculature is essential for reoxygenation of the blood, supplying oxygen for cellular respiration. Mitochondria have been proposed as the major oxygen sensing organelles in the pulmonary vasculature. Using electrophysiological techniques and immunofluorescence an interaction of the mitochondria with Kv channels was investigated. Inhibitors, blocking the mitochondrial electron transport chain at different complexes were shown to have a dual effect on Kv currents in freshly isolated rat pulmonary arterial smooth muscle cells (PASMCs). These dual effects comprised of an enhancement of Kv current in a negative potential range (manifested as a 5-14 mV shift in the Kv activation to more negative membrane voltages) with a decrease in current amplitude at positive potentials. Such effects were most prominent as a result of inhibition of Complex III by antimycin A. Investigation of the mechanism of antimycin A-mediated effects on IKv revealed the presence of a mitochondrial-mediated Mg2+ and ATP dependent regulation of Kv channels in PASMCs, which exists in addition to that currently proposed to be caused by changes in intracellular reactive oxygen species.
