EFFECT OF CAMP AND ATP ON THE HYPERPOLARIZATION-ACTIVATED CURRENT IN MOUSE DORSAL-ROOT GANGLION NEURONS

In mouse dorsal root ganglion (DRG) neurons the activation curve of th e hyperpolarization-activated current (I-h) shifted towards depolarize d potentials when cAMP was present in the pipette. The relation betwee n the midpoint potential and cAMP concentration could be described by a Hill function with a half-maximal concentration of 0.55 mu M cAMP, r eflecting a direct action of cAMP on the channel. With 5 mM ATP and a saturating concentration of cAMP an additional shift of the midpoint p otential is observed which can be explained by phosphorylation. Applic ation of Rp-cAMPS and Sp-cAMPS support the hypothesis of both a phosph orylation pathway and a direct effect exhibited by these molecules. Th e bell-shaped curves, relating the time constants for the slow and fas t current components to the voltage, shifted towards positive membrane potentials when cAMP and ATP were in the pipette. The fully activated I-h/voltage relation and the reversal potential were not dependent on the presence of cAMP or ATP in the pipette. The mean resting membrane potential of -59 mV, using the perforated-patch configuration, hyperp olarized in the presence of extracellular CsCl. In the whole-cell conf iguration the resting membrane potential was significantly more negati ve at 0 mu M cAMP (-61 mV) than at 100 mu M cAMP (-57 mV). Thus, the a ctivation of I-h, regulated by both the intracellular cAMP and the ATP concentration, may influence the excitability of DRG neurons.