Adenosine A1 receptor‐operated calcium entry in renal afferent arteriolar smooth muscle cells is dependent on postnatal maturation of canonical transient receptor potential isoform 3 channels

Abstract

Adenosine, a regulator of cardiovascular development and renal function constricts renal afferent arterioles by activating its cognate A1 receptors (AA1Rs). Activation of AA1Rs elevates intracellular Ca2+ ([Ca2+]i) concentration in renal vascular smooth muscle cells, mechanisms of which are not fully resolved. Whether AA1R expression and function in preglomerular microvessels are dependent on postnatal kidney maturation are also unclear. Here, we show that selective activation of AA1R by 2‐chloro‐N6‐cyclopentyladenosine (CCPA) does not stimulate store‐operated Ca2+ entry in afferent arterioles isolated from infant pigs. However, CCPA‐induced [Ca2+]i elevation is dependent on phospholipase C, protein kinase C, and canonical transient receptor potential isoform 3 (TRPC3) channels. The basal [Ca2+]i concentration was unchanged in afferent arterioles isolated from newly farrowed (0 day) pigs when compared with their 20‐day old counterparts. Whereas, CCPA‐induced [Ca2+]i elevation was ~ 43% larger in afferent arterioles from 20‐day old pigs. AA1R protein expression levels in the kidneys and afferent arterioles were unaltered in 0‐day versus 20‐day old pigs. By contrast, TRPC3 channel protein expression was ~ 92 and 78% higher in 20‐day old pig kidneys and afferent arterioles, respectively. These data suggest that activation of AA1Rs elicits receptor‐operated Ca2+ entry in porcine afferent arterioles, an effect dependent on postnatal maturation of TRPC3 channels.Support or Funding InformationNIH R01 DK101668