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- Title
T-type voltage-gated calcium channels regulate the tone of mouse efferent arterioles.
- Authors
Poulsen, Christian B.; Al-Mashhadi, Rozh H.; Cribbs, Leanne L.; Skøtt, Ole; Hansen, Pernille B.
- Abstract
Voltage-gated calcium channels are important for the regulation of renal blood flow and the glomerular filtration rate. Excitation-contraction coupling in afferent arterioles is known to require activation of these channels and we studied their role in the regulation of cortical efferent arteriolar tone. We used microdissected perfused mouse efferent arterioles and found a transient vasoconstriction in response to depolarization with potassium; an effect abolished by removal of extracellular calcium. The T-type voltage-gated calcium channel antagonists mibefradil and nickel blocked this potassium-induced constriction. Further, constriction by the thromboxane analogue U46619 was significantly inhibited by mibefradil at a concentration specific for T-type channels. Using PCR, we found that two channel subtypes, Cav3.1 and Cav3.2, were expressed in microdissected efferent arterioles. Cav3.1 was found by immunocytochemistry to be located in mouse efferent arterioles, human pre- and postglomerular vasculature, and Cav3.2 in rat glomerular arterioles. Inhibition of endothelial nitric oxide synthase by L-NAME or its deletion by gene knockout changed the potassium-elicited transient constriction to a sustained response. Low concentrations of nickel, an agent that blocks Cav3.2, had a similar effect. Thus, T-type voltage-gated calcium channels are functionally important for depolarization-induced vasoconstriction and subsequent dilatation in mouse cortical efferent arterioles.
- Subjects
EFFECT of drugs on calcium channels; REGULATION of blood circulation; GLOMERULAR filtration rate; VASOCONSTRICTION; MIBEFRADIL (Drug); IMMUNOCYTOCHEMISTRY; LABORATORY mice
- Publication
Kidney International, 2011, Vol 79, Issue 4, p443
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.2010.429