부산대학교 도서관

AIM:: Using mice deficient in the CaV3.1 T-type Ca channel, the aim of the present study was to elucidate the molecular identity of non-L-type channels involved in vascular tone regulation in mesenteric arteries and arterioles. METHODS:: We used immunofluorescence microscopy to localize CaV3.1 channels, patch clamp electrophysiology to test the effects of a putative T-type channel blocker NNC 55-0396 on whole-cell Ca currents, pressure myography and Ca imaging to test diameter and Ca responses of the applied vasoconstrictors, and Q-PCR to check mRNA expression levels of several Ca handling proteins in wild-type and CaV3.1 mice. RESULTS:: Our data indicated that CaV3.1 channels are important for the maintenance of myogenic tone at low pressures (40–80 mm Hg), whereas they are not involved in high-voltage-activated Ca currents, Ca entry or vasoconstriction to high KCl in mesenteric arteries and arterioles. Furthermore, we show that NNC 55–0396 is not a specific T-type channel inhibitor, as it potently blocks L-type and non-L-type high-voltage-activated Ca currents in mouse mesenteric vascular smooth muscle cell. CONCLUSION:: Our data using mice deficient in the CaV3.1 T-type channel represent new evidence for the involvement of non-L-type channels in arteriolar tone regulation. We showed that CaV3.1 channels are important for the myogenic tone at low arterial pressure, which is potentially relevant under resting conditions in vivo. Moreover, CaV3.1 channels are not involved in Ca entry and vasoconstriction to large depolarization with, for example, high KCl. Finally, we caution against using NNC 55–0396 as a specific T-type channel blocker in native cells expressing high-voltage-activated Ca channels.