Adenosine potentiates the delayed-rectifier potassium conductance but has no effect on the hyperpolarization-activated I sub(h) current in frog melanotrophs

The effects of adenosine on the voltage-sensitive delayed-rectifier K super(+) (I sub(K)) currents and hyperpolarization-activated cationic inward current (I sub(h)) were studied in cultured frog melanotrophs using the whole-cell configuration of the patch-clamp technique. The A sub(1) receptor agonist R-N-6-phenylisopropyl-adenosine (R-PIA; 50 mu M) reversibly increased I sub(K). Perfusion of dibutyryl-cAMP (1 mM) in the external solution did not modify the R-PIA-induced enhancement of I sub(K). Pretreatment of melanotrophs with pertussis toxin (1 mu g/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 sub(h)-like conductance. This conductance was characterized by a high K super(+) selectivity and a low Na super(+) permeability and was resistant to tetrodotoxin (1 mu M). R-PIA had no effect on I sub(h). The present study demonstrates that in frog melanotrophs adenosine inhibits the electrical activity by activating I sub(K) through an A sub(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 sub(h) conductance in frog melanotrophs which is not modulated by A sub(1) receptors.