ADENOSINE POTENTIATES THE DELAYED-RECTIFIER POTASSIUM CONDUCTANCE BUTHAS NO EFFECT ON THE HYPERPOLARIZATION-ACTIVATED I-H CURRENT IN FROG MELANOTROPHS

The effects of adenosine on the voltage-sensitive delayed-rectifier K (I-K) currents and hyperpolarization-activated cationic inward curren t (I-h) were studied in cultured frog melanotrophs using the whole-cel l configuration of the patch-clamp technique. The A(1) receptor agonis t R-N-6-phenylisopropyl-adenosine (R-PIA; 50 mu M) reversibly increase d 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 mela notrophs with pertussis toxin (1 mu g/ml; 12 h) totally abolished the R-PLA-evoked response. Application of hyperpolarizing voltage pulses f rom -60 to -120 mV to melanotrophs induced a two-component inward curr ent corresponding to an I-h-like conductance. This conductance was cha racterized by a high K+ selectivity and a low Na+ permeability and was resistant to tetrodotoxin (1 mu M). R-PIA had no effect on I-h. The p resent study demonstrates that in frog melanotrophs adenosine inhibits the electrical activity by activating I-K through an A(1) receptor su btype coupled to a pertussis toxin-sensitive pathway independent of th e cAMP/PKA system. This study also demonstrates the existence of a I-h conductance in frog melanotrophs which is not modulated by A(1) recep tors. (C) 1998 Elsevier Science B.V. All rights reserved.