Purinoreceptor‐mediated current in myocytes from renal resistance arteries

Background and purpose:  Ionotropic purinoreceptors (P2X) in renal vascular smooth muscle cells (RVSMCs) are involved in mediating the sympathetic control and paracrine regulation of renal blood flow (RBF). Activation of P2X receptors elevates [Ca 2+ ] i in RVSMCs triggering their contraction, leading to renal vasoconstriction and decrease of RBF. The goal of the present work was to characterize the P2X receptor‐mediated ionic current (I P2X ) and to identify the types of P2X receptors expressed in myocytes isolated from interlobar and arcuate arteries of rat kidney. Experimental approach:  The expression of P2X receptors in isolated RVSMCs was analysed by reverse transcription (RT)–PCR. I P2X and membrane potential were recorded using the amphotericin B‐perforated patch method. Key results:  RT–PCR analysis on single RVSMCs showed the presence of genes encoding P2X1 and P2X4 receptors. Under voltage clamp conditions, the selective P2X receptor agonist αβ‐methylene ATP (αβ‐meATP) evoked I P2X similar to that induced by ATP. Under current clamp conditions, both ATP and αβ‐meATP evoked a spike‐like membrane depolarization followed by a sustained depolarization, linking P2X receptors in RVSMCs to sympathetic control of renal vascular tone. A selective antagonist of P2X1 receptors, NF279, reduced I P2X amplitude by ∼65% concentration‐dependently manner within the nanomolar to sub‐micromolar range. The residual current was resistant to micromolar concentrations of NF279, but was inhibited by sub‐millimolar to millimolar concentrations of NF279. Conclusions and implications:  Two types of functional P2X receptors, monomeric P2X1 and heteromeric P2X1/4 receptors, are expressed in RVSMCs. Our study has identified important targets for possible pharmacological intervention in the sympathetic control of renal circulation. British Journal of Pharmacology (2010) 160, 987–997; 10.1111/j.1476‐5381.2010.00714.x