Identification of L- and T-type Ca channels in rat cerebral arteries: role in myogenic tone development

El-Rahman RR, Harraz OF, Brett SE, Anfinogenova Y, Mufti RE, Goldman D, Welsh DG. Identification of Land T-type Ca channels in rat cerebral arteries: role in myogenic tone development. Am J Physiol Heart Circ Physiol 304: H58–H71, 2013. First published October 26, 2012; doi:10.1152/ajpheart.00476.2012.— L-type Ca 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 Ca channels are not singularly expressed in vascular tissue and that other subtypes are likely present. In this study, we ascertained which voltage-gated Ca channels are expressed in rat cerebral arterial smooth muscle and determined their contribution to the myogenic response. mRNA analysis revealed that the 1-subunit of L-type (Cav1.2) and T-type (Cav3.1 and Cav3.2) Ca 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 Ba currents were isolated and each were shown to retain electrical characteristics consistent with Land T-type Ca channels. The nifedipine-insensitive Ba current was blocked by mibefradil, kurtoxin, and efonidpine, T-type Ca channel inhibitors. Pressure myography revealed that L-type Ca 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 Ca 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 Ca blockade could alter arterial flow by 20–50%. Overall, our findings indicate that Land T-type Ca 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.