K+, at concentrations reached in the extracellular space during neuronal activity (5-10 mM), promotes a time- and concentration-dependent hydrolysis of [3H]glycogen newly synthesized by mouse cerebral cortical slices. In the present study, the glycogenolytic action of K+ was examined in the neocortex of the quaking mouse, a spontaneously epileptic mutant characterized by deficient myelination of the CNS. The potency and efficacy of K+ in eliciting glycogen hydrolysis was greatly enhanced in cerebral cortical slices prepared from homozygous quaking mice (qk/qk) older than 7 weeks of age, indicating a supersensitive response to a metabolic action of the ion. A detailed ontogenic analysis showed an evolution of the supersensitive response to K+ which is reminiscent of the previously described increase in the number of alpha 2-adrenoreceptors in the brainstem of this mutant. In contrast to the altered response to K+, the glycogenolytic action of noradrenaline and vasoactive intestinal peptide reported earlier was equally expressed in qk/qk and in their unaffected littermates.