HEPARIN PREVENTS M-CURRENT OVER-RECOVERY BUT NOT M-CURRENT SUPPRESSION IN BULLFROG SYMPATHETIC-GANGLION NEURONS

The excitatory actions of G-protein-coupled agonists on amphibian sympathetic ganglion cells involve suppression of a voltage and time dependent, non-inactivating K+-current called the M-current. Suppression of this current by muscarine or peptides is followed by a phase of 'over-recovery' during which the M-current exceeds its original level. Whilst it has been suggested that release of intracellular Ca2+ following the agonist-induced liberation of inositol 1,4,5-trisphosphate is involved in the suppression phase of the response, another hypothesis suggests that the agonist-induced elevation of intracellular Ca2+ may account for M-current 'over-recovery'. The present study supports the latter hypothesis because intracellular application of the inositol 1,4,5-trisphosphate antagonist, heparin (150 muM), had little or no effect on muscarine-induced M-current suppression whilst the 'over-recovery' phase of the response was markedly attenuated.