Activity-dependent calpain activation plays a critical role in synaptic facilitation and post-tetanic potentiation.
Synaptic facilitation and post-tetanic potentiation (PTP) are believed to necessitate active regeneration of the release machinery and supply of synaptic vesicles to a ready-releasable site. The prevailing hypothesis assumes that synapsins play pivotal roles in these processes. Using a cholinergic synapse formed between cultured Aplysia neurons (B2 and MCn), we demonstrate here that the calcium-activated protease-calpain serves as a major regulating element in the cascade that links electrical activity, elevation of the free intracellular calcium concentration, and short-term synaptic enhancements such as facilitation and PTP. Our study revealed that calpain inhibitors (calpeptin and MG132) transform a facilitating synapse into a depressing one, and reduce its PTP by 80.6%. Inhibition of CaM kinases, PKA, and MAPK also reduced PTP at this synapse. When inhibitors of these kinases were applied together with calpeptin, tetanic stimuli led to synaptic depression. We concluded that at this synapse facilitation and PTP are mediated mainly by the calpain-dependent processes and to a smaller extent by the CaMKs/PKA/MAPK-dependent cascades.
Khoutorsky
Arkady
A
Department of Neurobiology, The Life Sciences Institute, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Spira
Micha E
ME
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001048:Aplysia / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors / Q000502:physiology*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004558:Electric Stimulation; D004594:Electrophysiology; D004789:Enzyme Activation / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000502:physiology*; D016704:Synapsins / Q000378:metabolism
D016704:Synapsins; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D002154:Calpain; D000109:Acetylcholine