Loss of cerebrovascular Shaker-type K+ channels: A shared vasodilator defect of genetic and renal hypertensive rats

Ann A. Tobin, Biny K. Joseph, Hamood N. Al-Kindi, Sulayma Albarwani, Jane A. Madden, Leah T. Nemetz, Nancy J. Rusch, Sung W. Rhee

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The cerebral arteries of hypertensive rats are depolarized and highly myogenic, suggesting a loss of K+ channels in the vascular smooth muscle cells (VSMCs). The present study evaluated whether the dilator function of the prominent Shaker-type voltage-gated K+ (KV1) channels is attenuated in middle cerebral arteries from two rat models of hypertension. Block of KV1 channels by correolide (1 μmol/l) or psora-4 (100 nmol/l) reduced the resting diameter of pressurized (80 mmHg) cerebral arteries from normotensive rats by an average of 28 ± 3% or 26 ± 3%, respectively. In contrast, arteries from spontaneously hypertensive rats (SHR) and aortic-banded (Ao-B) rats with chronic hypertension showed enhanced Ca2+-dependent tone and failed to significantly constrict to correolide or psora-4, implying a loss of KV1 channel-mediated vasodilation. Patch-clamp studies in the VSMCs of SHR confirmed that the peak K+ current density attributed to KV1 channels averaged only 5.47 ± 1.03 pA/pF, compared with 9.58 ± 0.82 pA/pF in VSMCs of control Wistar-Kyoto rats. Subsequently, Western blots revealed a 49 ± 7% to 66 ± 7% loss of the pore-forming α1.2- and α1.5-subunits that compose KV1 channels in cerebral arteries of SHR and Ao-B rats compared with control animals. In each case, the deficiency of KV1 channels was associated with reduced mRNA levels encoding either or both α-subunits. Collectively, these findings demonstrate that a deficit of α1.2- and α1.5- subunits results in a reduced contribution of KV1 channels to the resting diameters of cerebral arteries from two rat models of hypertension that originate from different etiologies.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume297
Issue number1
DOIs
Publication statusPublished - Jul 2009

Keywords

  • Cerebral arteries
  • Hypertension
  • Potassium channels
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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