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

Abstract

Abstract-Voltage-gated K ϩ currents play an important role in determining membrane potential, intracellular Ca 2ϩ , and contraction in arterial smooth muscle. In this study, the expression of genes encoding voltage-gated K ϩ 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 Kv␤1.1 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 Kv␤2.1 was observed in either strain. Kv1.2 and Kv1.5 transcripts represent Ϸ1 to 2 parts/10 5 of total mesenteric arterial RNA with Ϸ2-to 5-fold lower levels in aorta and tail artery. Whole-cell voltage-gated K ϩ channel currents, recorded from mesenteric arterial myocytes, were larger in SHR than WKY (eg, at 0 mV: 7.3Ϯ0.8 versus 10.9Ϯ1.2 pA/pF). The voltage dependence of activation was more negative in SHR (V 0.5 : Ϫ20Ϯ4 mV versus Ϫ32Ϯ3 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 Kv␤1.1). These differences in gene expression are associated with a greater voltage-gated K ϩ 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.

The T-type Ca2+ Channel Inhibitor Mibefradil Inhibits Voltage-Dependent K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells

“…During hypertension, decreased expression and function of Kv channels in conjunction with membrane depolarization were observed in most systemic arteries (17,18). Similar to hypertension, reduced Kv channel expression and function have also been reported in chronic hypoxic and diabetic condition (19,20).…”

Molecular Composition of 4-Aminopyridine-Sensitive Voltage-Gated K + Channels of Vascular Smooth Muscle

“…10 -16,36 -39 Moreover, transcripts encoding Kv␤ subunits were also shown to be expressed in smooth muscle of pulmonary artery, mesenteric artery, and gastrointestinal tract. 10,12,13,38 However, Kv1.1, Kv1.3, and Kv1.6 were reported to be expressed in pulmonary 10 and/or mesenteric arteries, 12,13 but were not detected in RPV. Additionally, splice variants of Kv␤1 (ie, ␤1.1 and ␤1.2) were found in smooth muscle cells of the gastrointestinal tract, but ␤2.1 expression was not detected.…”

Differential activation of potassium channels in cerebral and hindquarter arteries of rats during simulated microgravity

“…Patch-clamp evidence has been obtained in VSMCs from mesenteric (9,10,41), renal (36), and cerebral (32,45,55) arteries. Upregulation of mRNA encoding Kv␣1.2 and increases in K v ␣1.3 and K v ␤1.1 transcript level were found in SHR systemic arteries (8). Increased expression of the BK Ca ␣-subunit at the protein level, but not the transcript level, has been observed in systemic VSMCs of SHR (11).…”