Myogenic tone is impaired at low arterial pressure in mice deficient in the low-voltage-activated CaV 3.1 T-type Ca(2+) channel.
OBJECTIVE
Using mice deficient in the CaV 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 CaV 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 CaV 3.1(-/-) mice.


RESULTS
Our data indicated that CaV 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 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(2+) currents in mouse mesenteric vascular smooth muscle cell.


CONCLUSIONS
Our data using mice deficient in the CaV 3.1 T-type channel represent new evidence for the involvement of non-L-type channels in arteriolar tone regulation. We showed that CaV 3.1 channels are important for the myogenic tone at low arterial pressure, which is potentially relevant under resting conditions in vivo. Moreover, CaV 3.1 channels are not involved in Ca(2+) 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(2+) channels.
Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
K
K
Björling
H
H
Morita
M F
MF
Olsen
A
A
Prodan
P B
PB
Hansen
P
P
Lory
N-H
NH
Holstein-Rathlou
L J
LJ
Jensen
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000172:deficiency* / Q000235:genetics; D003521:Cyclopropanes / Q000494:pharmacology; D004195:Disease Models, Animal; D007022:Hypotension / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009281:Naphthalenes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
D001562:Benzimidazoles; C498197:Cacna1g protein, mouse; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D003521:Cyclopropanes; D009281:Naphthalenes; C484287:NNC 55-0396; D002118:Calcium