Identification of L- and T-type Ca2+ channels in rat cerebral arteries: Role in myogenic tone development

Rasha R. Abd El-Rahman, Osama F. Harraz, Suzanne E. Brett, Yana Anfinogenova, Rania E. Mufti, Daniel Goldman, Donald G. Welsh

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

Abstract

L-type Ca2+ channels are broadly expressed in arterial smooth muscle cells, and their voltage-dependent properties are important in tone development. Recent studies have noted that these Ca2+ channels are not singularly expressed in vascular tissue and that other subtypes are likely present. In this study, we ascertained which voltage-gated Ca2+ channels are expressed in rat cerebral arterial smooth muscle and determined their contribution to the myogenic response. mRNA analysis revealed that the α1-subunit of L-type (Cav1.2) and T-type (Cav3.1 and Cav3.2) Ca2+ channels are present in isolated smooth muscle cells. Western blot analysis subsequently confirmed protein expression in whole arteries. With the use of patch clamp electrophysiology, nifedipine-sensitive and -insensitive Ba2+ currents were isolated and each were shown to retain electrical characteristics consistent with L- and T-type Ca2+ channels. The nifedipine-insensitive Ba2+ current was blocked by mibefradil, kurtoxin, and efonidpine, T-type Ca2+ channel inhibitors. Pressure myography revealed that L-type Ca2+ channel inhibition reduced tone at 20 and 80 mmHg, with the greatest effect at high pressure when the vessel is depolarized. In comparison, the effect of T-type Ca2+ channel blockade on myogenic tone was more limited, with their greatest effect at low pressure where vessels are hyperpolarized. Blood flow modeling revealed that the vasomotor responses induced by T-type Ca2+ blockade could alter arterial flow by ~20-50%. Overall, our findings indicate that L- and T-type Ca2+ channels are expressed in cerebral arterial smooth muscle and can be electrically isolated from one another. Both conductances contribute to myogenic tone, although their overall contribution is unequal.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume304
Issue number1
DOIs
Publication statusPublished - 1 Jan 2013
Externally publishedYes

Keywords

  • Ca regulation
  • Myogenic tone
  • Vascular smooth muscle cells
  • Voltage-gated Ca channels

ASJC Scopus subject areas

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

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