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

The effects of adenosine on the voltage-sensitive delayed-rectifier K+ (IK) currents and hyperpolarization-activated cationic inward current (Ih) were studied in cultured frog melanotrophs using the whole-cell configuration of the patch-clamp technique. The A1 receptor agonist R-N6-phenylisopropyl-adenosine (R-PIA; 50 microM) reversibly increased IK. Perfusion of dibutyryl-cAMP (1 mM) in the external solution did not modify the R-PIA-induced enhancement of IK. Pretreatment of melanotrophs with pertussis toxin (1 microg/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 Ih-like conductance. This conductance was characterized by a high K+ selectivity and a low Na+ permeability and was resistant to tetrodotoxin (1 microM). R-PIA had no effect on Ih. The present study demonstrates that in frog melanotrophs adenosine inhibits the electrical activity by activating IK through an A1 receptor subtype coupled to a pertussis toxin-sensitive pathway independent of the cAMP/PKA system. This study also demonstrates the existence of a Ih conductance in frog melanotrophs which is not modulated by A1 receptors.