Adenosine A1receptor-operated calcium entry in renal afferent arterioles is dependent on postnatal maturation of TRPC3 channels

Adenosine, a regulator of cardiovascular development and renal function, constricts renal afferent arterioles by inducing intracellular Ca 2+ concentration ([Ca 2+ ] i ) elevation in smooth muscle cells (SMCs) via activation of its cognate A 1 receptors (A 1 Rs). Mechanisms that underlie A 1 R-dependent [Ca 2+ ] i elevation in renal vascular SMCs are not fully resolved. Whether A 1 R expression and function in preglomerular microvessels are dependent on postnatal kidney maturation is also unclear. In this study, we show that selective activation of A 1 Rs by 2-chloro- N 6 -cyclopentyladenosine (CCPA) does not stimulate store-operated Ca 2+ entry in afferent arterioles isolated from neonatal pigs. However, CCPA-induced [Ca 2+ ] i elevation is dependent on phospholipase C and transient receptor potential cation channel, subfamily C, member 3 (TRPC3). Basal [Ca 2+ ] i was unchanged in afferent arterioles isolated from newborn (0-day-old) pigs compared with their 20-day-old counterparts. By contrast, CCPA treatment resulted in significantly larger [Ca 2+ ] i in afferent arterioles from 20-day-old pigs. A 1 R protein expression levels in the kidneys and afferent arterioles were unaltered in 0- vs. 20-day-old pigs. However, the TRPC3 channel protein expression level was ~92 and 78% higher in 20-day-old pig kidneys and afferent arterioles, respectively. These data suggest that activation of A 1 Rs elicits receptor-operated Ca 2+ entry in porcine afferent arterioles, the level of which is dependent on postnatal maturation of TRPC3 channels. We propose that TRPC3 channels may contribute to the physiology and pathophysiology of A 1 Rs.