T‐ and L‐type Calcium Channels Contribute to Myogenic Tone In Cerebral Arteries

Abstract

The study scrutinized which voltage‐operated Ca2+ channels are expressed in cerebral arterial smooth muscle cells, and what role they play in myogenic tone development. A broad RT‐PCR screen of α1 subunits revealed mRNA expression of L‐type (Cav1.2) and T‐type (Cav3.1, and Cav3.2) Ca2+ channels in cerebral arterial smooth muscle cells. Western blot analysis conducted on whole arteries subsequently showed that all 3 α1 subunits were present at the protein level with T‐type expression qualitatively greater than L‐type. An immunohistochemical analysis of whole arteries revealed that Cav1.2 was primarily expressed in perivascular nerves although some limited/punctuate labeling was observable in smooth muscle. In contrast, the T‐type (Cav3.1, and Cav3.2) channels were robustly expressed in cerebral arterial smooth muscle and display defined periodicity. Functional measurements performed on cerebral arteries pressurized to 80 mmHg revealed that L‐type Ca2+ channels blockers, such as nifidipine (50–300nM) partially attenuate myogenic tone although a near complete blockade was achievable with the further addition of Mibefradil (300nm–1μM), a T‐type Ca2+ channel blocker. Cumulatively, these findings indicate that both L‐ and T‐type Ca2+ channels are expressed in cerebral arterial smooth muscle cells and that both Ca2+ channels play an important role in establishing myogenic tone in small cerebral arteries. These findings have important conceptual and therapeutic implications particularly as it relates to the treatment of cerebrovascular diseases. Supported by CIHR.