Renal function in T‐type voltage‐gated calcium channel knock‐out mice

Abstract

T‐type voltage‐gated calcium channels (Cav) are expressed in renal resistance vessels and collecting duct and calcium channels play an essential role in regulation of renal blood flow and glomerular filtration rate. The objective of the present study was to investigate renal function in two T‐type calcium channel knock‐out (KO) mice strains (Cav3.1 and Cav3.2). Continuous recordings of blood pressure (MAP), heart rate and inulin clearance (GFR) were performed in Wt and Cav3.1 and Cav3.2 KO mice using indwelling catheters. The night heart rate was significant lower in Cav3.1 KO compared to Wt with no difference in MAP. GFR was significantly higher in Cav3.2 KO compared to Wt. GFR in Cav3.1 KO were indistinguishable from Wt. No significant difference was observed in water intake, diuresis and electrolyte excretion measured before and after 24 hour water deprivation comparing Wt and Cav3.1 KO mice however a significant increase in sodium excretion rate was observed in both strains after water deprivation. We tested whether the high GFR in Cav3.2 KO was related to an increased contractility of the efferent arteriole in isolated perfused efferent arterioles. However depolarization and endothelin‐1 induced significant and similar constriction in Wt, Cav3.1 and Cav3.2 KO mice. In conclusion, lack of Cav3.1 is associated with a decreased heart rate whereas lack of Cav3.2 T‐type channels is associated with an increased GFR.Research Support: Lundbeck Foundation, The Danish Medical Research Council, The Danish Heart Foundation