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Myogenic tone is impaired at low arterial pressure in mice deficient in the low‐voltage‐activated C a V 3.1 T ‐type C a 2+ channel
Author(s) -
Björling K.,
Morita H.,
Olsen M. F.,
Prodan A.,
Hansen P. B.,
Lory P.,
HolsteinRathlou N.H.,
Jensen L. J.
Publication year - 2013
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12066
Subject(s) - mesenteric arteries , vasoconstriction , myogenic contraction , electrical impedance myography , chemistry , vascular smooth muscle , medicine , patch clamp , endocrinology , electrophysiology , anatomy , artery , vasodilation , smooth muscle
Aim Using mice deficient in the Ca V 3.1 T‐type Ca 2+ 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 Ca V 3.1 channels, patch clamp electrophysiology to test the effects of a putative T‐type channel blocker NNC 55‐0396 on whole‐cell Ca 2+ currents, pressure myography and Ca 2+ imaging to test diameter and Ca 2+ responses of the applied vasoconstrictors, and Q‐PCR to check mRNA expression levels of several Ca 2+ handling proteins in wild‐type and Ca V 3.1 −/− mice. Results Our data indicated that Ca V 3.1 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 2+ currents, Ca 2+ entry or vasoconstriction to high KC l 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 2+ currents in mouse mesenteric vascular smooth muscle cell. Conclusion Our data using mice deficient in the Ca V 3.1 T‐type channel represent new evidence for the involvement of non‐L‐type channels in arteriolar tone regulation. We showed that Ca V 3.1 channels are important for the myogenic tone at low arterial pressure, which is potentially relevant under resting conditions in vivo . Moreover, Ca V 3.1 channels are not involved in Ca 2+ entry and vasoconstriction to large depolarization with, for example, high KC l. Finally, we caution against using NNC 55–0396 as a specific T‐type channel blocker in native cells expressing high‐voltage‐activated Ca 2+ channels.