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 omega-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.
Hof
P R
PR
Département de Pharmacologie, Centre Médical Universitaire, Geneva, Switzerland.
Pascale
E
E
Magistretti
P J
PJ
D000818:Animals; D001696:Biomechanical Phenomena; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006868:Hydrolysis; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009474:Neurons / Q000502:physiology*; D009994:Osmolar Concentration; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D013757:Tetraethylammonium Compounds; D013779:Tetrodotoxin; D010042:Ouabain; D019789:Tetraethylammonium; D006003:Glycogen; D011188:Potassium