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.

Differential expression of KV channel α- and β-subunits in the bovine pulmonary arterial circulation

“…2, the intensity of Kv1.5 immunostaining appeared to be modestly greater in resistance than in conduit pulmonary arteries. In contrast to Archer et al (3), we, like McCulloch et al (22), found no evidence of K ϩ channel heterogeneity within the vascular wall of either conduit or resistance vessels (Figs. 2 and 3).…”

“…2 and 3). This does not rule out heterogeneous expression of subunits that were not examined; however, our results support the more recent data of McCulloch et al (22).…”

“…The regional heterogeneity in response to hypoxia within the pulmonary circulation could reflect the differential expression of K ϩ channel subtypes between conduit and resistance vessels. Previous electrophysiological studies in the rat (1,2) and rabbit (22) pulmonary vasculatures demonstrated K ϩ channel current heterogeneity between cells isolated from the conduit pulmonary arteries and those cells isolated from resistance-size vessels.…”

Contractile and electrophysiological properties of pulmonary artery smooth muscle are not altered in TASK‐1 knockout mice

“…The disparity between the pharmacology of I KV and the resting potential suggests that it is not the underlying K + current. Moreover, I KV density was comparable with PASMCs from other species, including rat (Manoury et al 2009), rabbit (McCulloch et al 2000), pig (Evans et al 1998) and human (Shimoda et al 2001 b ).…”

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

“…The predominant site of hypoxic pulmonary vasoconstriction (HPV) in the lung appears to be in the small pulmonary resistance arteries (< 200-300 μm diameter) (Shirai et al, 1986;Kato and Staub, 1996). These regional differences between conduit and resistance PASMCs may reflect distributional differences in Kv and BKCa channels (Archer et al, 1996McCulloch et al, 2000;Smirnov et al, 2002;. For example, conduit PASMCs predominantly express BKCa channels, which results in more sensitive inhibition by TEA or the specific BKCa channel blocker, charybdotoxin (Garcia et al, 1991).…”