Adenosine potentiates the delayed-rectifier potassium conductance but has no effect on the hyperpolarization-activated Ih current in frog melanotrophs

Abstract

The effects of adenosine on the voltage-sensitive delayed-rectifier K + ( I K) currents and hyperpolarization-activated cationic inward current ( I h) were studied in cultured frog melanotrophs using the whole-cell configuration of the patch-clamp technique. The A 1 receptor agonist R- N 6-phenylisopropyl-adenosine (R-PIA; 50 μM) reversibly increased I K. Perfusion of dibutyryl-cAMP (1 mM) in the external solution did not modify the R-PIA-induced enhancement of I K. Pretreatment of melanotrophs with pertussis toxin (1 μg/ml; 12 h) totally abolished the R-PIA-evoked response. Application of hyperpolarizing voltage pulses from −60 to −120 mV to melanotrophs induced a two-component inward current corresponding to an I h-like conductance. This conductance was characterized by a high K + selectivity and a low Na + permeability and was resistant to tetrodotoxin (1 μM). R-PIA had no effect on I h. The present study demonstrates that in frog melanotrophs adenosine inhibits the electrical activity by activating I K through an A 1 receptor subtype coupled to a pertussis toxin-sensitive pathway independent of the cAMP/PKA system. This study also demonstrates the existence of a I h conductance in frog melanotrophs which is not modulated by A 1 receptors.