Modulation of calcium currents in mammalian central serotoninergic neurones

The effect of phosphorylation on Ca<SUP>2+</SUP> current, in the presence and in the absence of 5-HT<SUB>1A</SUB> receptor activation, has been studied here using a whole-cell voltage-clamp technique in acutely dissociated adult rat DR neurones. In various neuronal preparatio...

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Bibliographic Details
Main Author: Hećimović, Hrvoje
Published: University of Edinburgh 1995
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Online Access:http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.652299
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Summary:The effect of phosphorylation on Ca<SUP>2+</SUP> current, in the presence and in the absence of 5-HT<SUB>1A</SUB> receptor activation, has been studied here using a whole-cell voltage-clamp technique in acutely dissociated adult rat DR neurones. In various neuronal preparations, transmitters have been shown to reduce voltage-dependent Ca<SUP>2+</SUP> currents. In DR neurones, the inhibitory action of 5-HT is incomplete, usually around 60%, and is accompanied by a dramatic slowing of the activation. 8-OH DPAT, a highly specific 5-HT<SUB>1A</SUB> agonist, also partially and reversibly reduces high-voltage activated (HVA) Ca<SUP>2+</SUP> currents and slows the activation time. It appears that the effect is G-protein mediated and it is believed that the G-protein acts directly on the Ca<SUP>2+</SUP> channel proteins, rather than through a freely diffusible second messenger. The action of 8-OH DPAT and GTP-γ-S on both the amplitude and the activation of the current can be removed by a large depolarising prepulse. A variety of data indicate that protein phosphorylation regulates the efficacy of synaptic transmission, both by controlling the release of neurotransmitters from the presynaptic nerve terminal and by modulating the sensitivity of receptors in the postsynaptic membrane. Presumably, at rest, some kind of phosphorylation/dephosphorylation balance exists. Evidence has been given that phosphorylation is a necessary step in ion channel functioning. It appears that inhibition of specific phosphatases, could potentiate already activated ion channel currents.