Adenosine A1 receptor-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 Ca2+ concentration ([Ca2+](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 [Ca2+](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 Ca2+ entry in afferent arterioles isolated from neonatal pigs. However, CCPA-induced [Ca2+](i) elevation is dependent on phospholipase C and transient receptor potential cation channel, subfamily C, member 3 (TRPC3). Basal [Ca2+](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 [Ca2+](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 similar to 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 Ca2+ 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.