A role for protein kinases and phosphatases in the Ca(2+)-induced enhancement of hippocampal AMPA receptor-mediated synaptic responses

Neuron. 1994 Sep;13(3):635-43. doi: 10.1016/0896-6273(94)90031-0.

Abstract

We have investigated the effects of inhibitors of protein kinases and protein phosphatases on the NMDA receptor-independent potentiation of evoked and miniature (m) excitatory postsynaptic currents (EPSCs) induced by the entry of Ca2+ via voltage-gated Ca2+ channels in hippocampal CA1 pyramidal neurons. Voltage pulse-induced potentiation was markedly attenuated when evoked in the presence of the protein kinase blockers KN-62, K-252a, or H-7. Bath application of the protein phosphatase inhibitor calyculin A converted the usual transient potentiation of both evoked and spontaneous EPSCs induced by voltage pulses into a more sustained potentiation. Similarly, the introduction of the phosphatase inhibitors microcystin LR or okadaic acid into postsynaptic cells, via patch pipettes, also resulted in a sustained increase in the amplitude of mEPSCs. We propose that entry of Ca2+ into CA1 neurons activates calcium/calmodulin-dependent protein kinase II, which leads to an enhanced responsiveness of synaptic AMPA receptor channels. The enhancement is transient, however, owing to postsynaptic phosphatase activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium / pharmacology*
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Electrophysiology
  • Ethers, Cyclic / pharmacology
  • Guinea Pigs
  • Hippocampus / physiology*
  • In Vitro Techniques
  • Male
  • Marine Toxins
  • Microcystins
  • Okadaic Acid
  • Oxazoles / pharmacology
  • Peptides, Cyclic / pharmacology
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphoric Monoester Hydrolases / physiology*
  • Protein Kinases / physiology*
  • Receptors, AMPA / physiology*
  • Synapses / physiology*

Substances

  • Ethers, Cyclic
  • Marine Toxins
  • Microcystins
  • Oxazoles
  • Peptides, Cyclic
  • Receptors, AMPA
  • Okadaic Acid
  • calyculin A
  • Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Phosphoprotein Phosphatases
  • Phosphoric Monoester Hydrolases
  • cyanoginosin LR
  • Calcium