Differential effect of T-type voltage-gated Ca2+ channel disruption on renal plasma flow and glomerular filtration rate in vivo

Voltage-gated Ca2+ (Cav) channels play an essential role in the regulation of renal blood flow and glomerular filtration rate (GFR). Because T-type Cav channels are differentially expressed in pre- and postglomerular vessels, it was hypothesized that they impact renal blood flow and GFR differentially. The question was addressed with the use of two T-type Cav knockout (Ca(v)3.1(-/-) and Ca(v)3.2(-/-)) mouse strains. Continuous recordings of blood pressure and heart rate, para-aminohippurate clearance (renal plasma flow), and inulin clearance (GFR) were performed in conscious, chronically catheterized, wild-type (WT) and Ca(v)3.1(-/-) and Ca(v)3.2(-/-) mice. The contractility of afferent and efferent arterioles was determined in isolated perfused blood vessels. Efferent arterioles from Ca(v)3.2(-/-) mice constricted significantly more in response to a depolarization compared with WT mice. GFR was increased in Ca(v)3.2(-/-) mice with no significant changes in renal plasma flow, heart rate, and blood pressure. Ca(v)3.1(-/-) mice had a higher renal plasma flow compared with WT mice, whereas GFR was indistinguishable from WT mice. No difference in the concentration response to K+ was observed in isolated afferent and efferent arterioles from Ca(v)3.1(-/-) mice compared with WT mice. Heart rate was significantly lower in Ca(v)3.1(-/-) mice compared with WT mice with no difference in blood pressure. T-type antagonists significantly inhibited the constriction of human intrarenal arteries in response to a small depolarization. In conclusion, Ca(v)3.2 channels support dilatation of efferent arterioles and affect GFR, whereas Ca(v)3.1 channels in vivo contribute to renal vascular resistance. It is suggested that endothelial and nerve localization of Ca(v)3.2 and Ca(v)3.1, respectively, may account for the observed effects.