Cholecystokinin induces a decrease in Ca²⁺ current in snail neurons that appears to be mediated by protein kinase C

Abstract

Three distinct classes of protein kinases have been shown to regulate Ca²⁺ current in excitable tissues. Cyclic AMP-dependent protein kinase mediates the action of noradrenaline on the Ca²⁺ current of cardiac muscle cells^1,2. Cyclic GMP-dependent protein kinase mediates the serotonin-induced modulation of the Ca²⁺ current in identified snail neurons³. The Ca²⁺/diacylglycerol-dependent protein kinase (protein kinase C) has also been found to regulate Ca²⁺ currents of neurons^4,5. However, no neurotrans-mitter has yet been shown to regulate Ca²⁺current through the activation of protein kinase C. We now report that cholecystokinin, a widely occurring neuropeptide⁶ which is present in molluscan neurons^7,8, modulates the Ca²⁺ current in identified neurons⁹ of the snail Helix aspersa, and that this effect appears to be mediated by protein kinase C. Specifically, sulphated cholecystokinin octapeptide 26–33 (CCK8), activators of protein kinase C, and intracellular injection of protein kinase C, all shorten the Ca²⁺-dependent action potential and decrease the amplitude of the Ca²⁺ current in these cells. All these effects are not reversible within the duration of the experiments. Moreover, intracellular injections of low concentrations of protein kinase C, which are ineffective by themselves, enhance the effectiveness of low concentrations of CCK8 on the Ca²⁺current.