K⁺ at concentrations reached in the extracellular space during neuronal activity promotes a Ca²⁺-dependent glycogen hydrolysis in mouse cerebral cortex

The effect of increasing [K⁺]₀ on ³H-glycogen levels was examined in mouse cerebral cortical slices. K⁺ stimulates in a time- and concentration-dependent manner the hydrolysis of ³H-glycogen. Over 70% of the maximal effect is reached within 30 sec and the EC₅₀ for the glycogenolytic action of K⁺ is 11 mM. Significant ³H-glycogen hydrolysis occurs at 5-12 mM [K⁺]₀, concentrations reached by the ion in the extracellular space during neuronal activity. The K⁺-evoked glycogenolysis is Ca²⁺-dependent, and is inhibited by Ca²⁺-channel blockers such as Ni²⁺ and Mn²⁺, but not by Cd²⁺, nifedipine, and ω-conotoxin. Furthermore, the effect of K⁺ is not enhanced by the Ca²⁺-channel agonist Bay K 8644. This type of pharmacological profile suggests that the activation of voltage-sensitive Ca²⁺ channels of the T subtype mediates the glycogenolytic action of K⁺. This set of observations suggests that K⁺ released in the extracellular space by active neurons may promote the mobilization of energy substrates and therefore play a role in the coupling between neuronal activity and energy metabolism.