cGMP-dependent protein kinase enhances Ca²⁺ current and potentiates the serotonin-induced Ca²⁺ current increase in snail neurones

Abstract

Protein phosphorylation catalysed by cyclic AMP-dependent^1,2, Ca²⁺/calmodulin-dependent³ and Ca²⁺/diacylglycerol-dependent⁴ protein kinases is important both in the modulation of synaptic transmission and in the regulation of neuronal membrane permeability (for reviews see refs ^5–7). However, there has previously been no evidence for the involvement of cyclic GMP-dependent protein kinase (cGMP-PK) in the regulation of neuronal function. Serotonin induces an increase of Ca²⁺ current in a group of identified ventral neurones of the snail Helix aspersa⁸ This effect is probably mediated by cGMP because it is mimicked by the intracellular injection of cGMP or the application of zaprinast⁸, an inhibitor of cGMP-dependent phosphodiesterase⁹. We have now found that the effect of either serotonin or zaprinast on the Ca²⁺ current is potentiated by the intracellular injection of cGMP-PK. Moreover, the intracellular injection of activated cGMP-PK (CGMP–PK+1 µM cGMP) greatly enhances the Ca²⁺ current of the identified ventral neurones seen in the absence of serotonin. These results indicate that cGMP-PK has a physiological role in the control of the membrane permeability of these neurones.