Differential regulation of action potential- and metabotropic glutamate receptor-induced Ca2+ signals by inositol 1,4,5-trisphosphate in dopaminergic neurons.

Guohong Cui, Brian E Bernier, Mark T Harnett, Hitoshi Morikawa

Waggoner Center for Alcohol and Addiction Research, Section of Neurobiology and Institute for Neuroscience, University of Texas, Austin, Texas 78712, USA.

The Journal of neuroscience : the official journal of the Society for Neuroscience 2007 Apr 25

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Ca2+ signals associated with action potentials (APs) and metabotropic glutamate receptor (mGluR) activation exert distinct influences on neuronal activity and synaptic plasticity. However, it is not clear how these two types of Ca2+ signals are differentially regulated by neurotransmitter inputs in a single neuron. We investigated this issue in dopaminergic neurons of the ventral midbrain using brain slices. Intracellular Ca2+ was assessed by measuring Ca2+-sensitive K+ currents or imaging the fluorescence of Ca2+ indicator dyes. Tonic activation of metabotropic neurotransmitter receptors (mGluRs, alpha1 adrenergic receptors, and muscarinic acetylcholine receptors), attained by superfusion of agonists or weak, sustained (approximately 1 s) synaptic stimulation, augmented AP-induced Ca2+ transients. In contrast, Ca2+ signals elicited by strong, transient (50-200 ms) activation of mGluRs with aspartate iontophoresis were suppressed by superfusion of agonists. These opposing effects on Ca2+ signals were both mediated by an increase in intracellular inositol 1,4,5-trisphosphate (IP3) levels, because they were blocked by heparin, an IP3 receptor antagonist, and reproduced by photolytic application of IP3. Evoking APs repetitively at low frequency (2 Hz) caused inactivation of IP3 receptors and abolished IP3 facilitation of single AP-induced Ca2+ signals, whereas facilitation of Ca2+ signals triggered by bursts of APs (five at 20 Hz) was attenuated by less than half. We further obtained evidence suggesting that the psychostimulant amphetamine may augment burst-induced Ca2+ signals via both depression of basal firing and production of IP3. We propose that intracellular IP3 tone provides a mechanism to selectively amplify burst-induced Ca2+ signals in dopaminergic neurons.

Citation

Guohong Cui, Brian E Bernier, Mark T Harnett, Hitoshi Morikawa. Differential regulation of action potential- and metabotropic glutamate receptor-induced Ca2+ signals by inositol 1,4,5-trisphosphate in dopaminergic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007 Apr 25;27(17):4776-85