Regional distribution of potassium currents in the rabbit pulmonary arterial circulation

Abstract

The response of pulmonary arteries to hypoxia varies as a function of vessel diameter. Small intrapulmonary resistance arteries are thought to be the main site of hypoxic pulmonary vasoconstriction (HPV), with hypoxia causing minimal contraction or even dilatation in large, conduit vessels. This has been proposed to reflect a differential distribution of morphologically and electrophysiologically distinct pulmonary artery smooth muscle (PASM) cells. We investigated longitudinal heterogeneity in smooth muscle cells isolated from five regions of the rabbit pulmonary vasculature and could find no evidence of morphological heterogeneity at the level of the light microscope. PASM cells from main (8 mm outer diameter) and branch (5 mm) arteries and large ( 400 m) intrapulmonary arteries (IPA) were similar in shape and size, as indicated by cell capacitance (25 pF). PASM cells from medium (200-400 m) and small ( 200 m) IPA were significantly smaller (15 pF), but had the same classical spindle shape. Cells from all five regions also had similar resting membrane potentials and displayed voltage-activated K+ currents of similar amplitude when recorded in standard physiological solution. Longitudinal heterogeneity in K+ current became apparent when tetraethylammonium ions (TEA; 10 mM) and glibenclamide (10 M) were added. The remaining delayed rectifier current (IK(V)) doubled in amplitude upon moving down the pulmonary arterial tree from the main artery (9 pA pF-1 at 40 mV) to the large IPA (17 pA pF-1), but remained constant throughout the intrapulmonary vasculature. The O2-sensitive, non-inactivating K+ current (IK(N)) showed a similar trend, but was significantly reduced in the smallest IPA, where its amplitude was comparable with the main artery. Thus the IK(N)/IK(V) ratio was relatively constant, at around 0.14, from the main pulmonary artery to medium IPA, but fell by 50% in the smallest vessels. The amplitude of the TEA-sensitive K+ current was similar (16 pA pF-1 at 40 mV) at all levels of the pulmonary arterial tree, except in the medium sized vessels where it was 50% smaller. These variations in K+ current expression correlate with reported variations in sensitivity to hypoxia and may contribute to the regional heterogeneity of HPV in the rabbit lung.