Differential Expression of Voltage-Gated K + Channel Genes in Arteries From Spontaneously Hypertensive and Wistar-Kyoto Rats

Abstract

Abstract —Voltage-gated K + currents play an important role in determining membrane potential, intracellular Ca 2+ , and contraction in arterial smooth muscle. In this study, the expression of genes encoding voltage-gated K + channels of the Kv1.X family was compared in arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Expression of Kv1.X in thoracic aorta, mesenteric arteries, tail artery, and heart was determined, both qualitatively and quantitatively, by reverse transcription–polymerase chain reaction. Our results demonstrate distinct but overlapping patterns of expression in vascular tissues. In general, Kv1.2 and Kv1.5 were most highly represented, and the levels of Kv1.2 were significantly larger in all tissues from SHR. Levels of Kv1.5 in arteries did not differ significantly between strains but were greater in SHR heart. Moderate levels of Kv1.3 and Kvβ1.1 expression were also found in all tissues and were larger in SHR. Kv1.1 expression was not different between the 2 strains, and no significant expression of Kv1.4 (except in heart and aorta), Kv1.6, or Kvβ2.1 was observed in either strain. Kv1.2 and Kv1.5 transcripts represent ≈1 to 2 parts/10 5 of total mesenteric arterial RNA with ≈2- to 5-fold lower levels in aorta and tail artery. Whole-cell voltage-gated K + channel currents, recorded from mesenteric arterial myocytes, were larger in SHR than WKY (eg, at 0 mV: 7.3±0.8 versus 10.9±1.2 pA/pF). The voltage dependence of activation was more negative in SHR (V 0.5 : −20±4 mV versus −32±3 mV) but that of availability was not different. These results indicate that Kv1.X genes are differentially expressed between WKY and SHR (especially Kv1.2 and Kvβ1.1). These differences in gene expression are associated with a greater voltage-gated K + channel current density in SHR and shifted voltage-dependent activation compared with WKY. These differences may be a compensatory mechanism related to the membrane potential depolarization in SHR or some manifestation thereof.