Myogenic tone is impaired at low arterial pressure in mice deficient in the low‐voltage‐activated CaV3.1 T‐type Ca2+ channel. (18th February 2013)

• Record Type: Journal Article
• Authors: Björling, K.; Morita, H.; Olsen, M. F.; Prodan, A.; Hansen, P. B.; Lory, P.; Holstein‐Rathlou, N.‐H.; Jensen, L. J.
• Is Part Of: Acta physiologica. Volume 207:Number 4(2013:Apr.)
• Page Start: 709
• Page End: 720
• Publication Date: 2013-02-18
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12066
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" id="apha12066-abs-0001"> <title>Abstract</title> <sec id="apha12066-sec-0001" sec-type="section"> <title>Aim</title> <p>Using mice deficient in the Ca<sub>V</sub>3.1 T‐type Ca<sup>2+</sup> 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.</p> </sec> <sec id="apha12066-sec-0002" sec-type="section"> <title>Methods</title> <p>We used immunofluorescence microscopy to localize Ca<sub>V</sub>3.1 channels, patch clamp electrophysiology to test the effects of a putative T‐type channel blocker NNC 55‐0396 on whole‐cell Ca<sup>2+</sup> currents, pressure myography and Ca<sup>2+</sup> imaging to test diameter and Ca<sup>2+</sup> responses of the applied vasoconstrictors, and Q‐PCR to check mRNA expression levels of several Ca<sup>2+</sup> handling proteins in wild‐type and Ca<sub>V</sub>3.1<sup>−/−</sup> mice.</p> </sec> <sec id="apha12066-sec-0003" sec-type="section"> <title>Results</title> <p>Our data indicated that Ca<sub>V</sub>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<sup>2+</sup> currents, Ca<sup>2+</sup> 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<sup>2+</sup> currents in mouse mesenteric vascular smooth muscle cell.</p> </sec> <sec id="apha12066-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Our data using mice deficient in the Ca<sub>V</sub>3.1 T‐type channel represent new evidence for the involvement of non‐L‐type channels in arteriolar tone regulation. We showed that Ca<sub>V</sub>3.1 channels are important for the myogenic tone at low arterial pressure, which is potentially relevant under resting conditions <italic>in vivo</italic>. Moreover, Ca<sub>V</sub>3.1 channels are not involved in Ca<sup>2+</sup> 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<sup>2+</sup> channels.</p> </sec> </abstract>