Electrophysiological and Pharmacological Characterization of K_ATP Channel Involved in the K⁺ Current Responses to FSH and Adenosine in the Follicular Cells of Xenopus Oocyte

Abstract

Follicular cells surrounding Xenopus oocyte under voltage-clamp produce K⁺ current responses to follicle stimulating hormone (FSH), Adenosine (Ade) and intracellularly applied cAMP. We previously reported that these responses are suppressed by the stimulation of P2Y-receptor through phosphorylation by PKC presumably of ATP-sensitive K⁺ (K_ATP) channel. The K_ATP channel comprises sulfonylurea receptor (SURs) and K⁺ ionophore (Kirs) having differential sensitivities to K⁺ channel openers (KCO) depending on the SURs. To characterize the K⁺ channels involved in the FSH-and Ade-induced responses, we investigated effects of various KCOs and SUR blockers on the agonist-induced responses. Applications of PCO-400, Cro, pinacidil but not diazoxide produced K⁺ current responses similar to the FSH- and Ade-induced responses in the magnitude order of PCO-400 > Cro >> pinacidil in favor of SUR2A. Application of glibenclamide, phentolamine and tolbutamide suppressed all the K⁺ current responses to FSH, Ade, cAMP, and KCOs. Furthermore, the both FSH- and Ade-induced responses were markedly augmented during the KCO-induced responses or vice versa. I–V curves for the K⁺ current responses induced by Cro, Ade and FSH showed outward rectification in normal [K⁺]_o but weak inward rectification in 122 mM [K⁺]_o. In addition, stimulations of P2Y receptor by UTP or PKC by PDBu markedly depressed the K⁺ current response to KCO in favor of Kir6.1, as previously observed with the responses to FSH and Ade. These results suggest that the K⁺ current responses to FSH and Ade may be produced by opening of a novel type of K_ATP channel comprising SUR2A and Kir6.1.