Apical P2Y4 purinergic receptor controls K+ secretion by vestibular dark cell epithelium

It was previously shown that K+ secretion by vestibular dark cell epithelium is under control of G protein-coupled receptors of the P2Y family in the apical membrane that are activated by both purine and uridine nucleotides (P2Y2, P2Y4, or P2Y6). The present study was conducted to determine the subtype of purinergic receptor and to test whether these receptors undergo desensitization. The transepithelial short-circuit current represents electrogenic K+ secretion and was found to be reduced by UTP, ATP, and diadenosine tetraphosphate, but not UDP. Neither pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, 30 microM) nor suramin (100 microM) inhibited the effect of UTP. The potencies of the agonists were consistent with rodent P2Y4 and P2Y2, but not P2Y6, receptors. The ineffectiveness of suramin was consistent with P2Y4, but not P2Y2. Transcripts for both P2Y2 and P2Y4 were found in vestibular labyrinth. Sustained exposure to ATP or UTP for 15 min caused a constant depression of short-circuit current with no apparent desensitization. The results support the conclusion that regulation of K+ secretion across vestibular dark cell epithelium occurs by P2Y4 receptors without desensitization of the response.