Voltage-gated calcium channels mediate intracellular calcium increase in weaver dopaminergic neurons during stimulation of D2 and GABAB receptors

Journal of Neurophysiology
Ezia GuatteoNicola B Mercuri

Abstract

The weaver (wv) mutation affects the pore-forming region of the inwardly rectifying potassium channel (GIRK) leading to degeneration of cerebellar granule and midbrain dopaminergic neurons. The mutated channel (wvGIRK) loses its potassium selectivity, allowing sodium (Na+) and possibly calcium ions (Ca2+) to enter the cell. Here we performed whole cell patch-clamp recordings combined with microfluorometry to investigate possible differences in calcium ([Ca2+]i) dynamics in native dopaminergic neurons (expressing the wvGIRK2 subunits) in the midbrain slice preparation from homozygous weaver (wv/wv) and control (+/+) mice. Under resting conditions, [Ca2+]i was similar in wv/wv compared with +/+ neurons. Activation of wvGIRK2 channels by D2 and GABAB receptors increased [Ca2+]i in wv/wv neurons, whereas activation of wild-type channels decreased [Ca2+]i in +/+ neurons. The calcium rise in wv/wv neurons was abolished by antagonists of the voltage-gated calcium channels (VGCC); voltage clamp of the neuron at -60 mV; and hyperpolarization of the neuron to -80 mV or more, in current clamp, and was unaffected by TTX. Therefore we propose that wvGIRK2 channels in native dopamine neurons are not permeable to Ca2+, and when activated by D...Continue Reading

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Citations

May 12, 2011·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Paul M A AntonyRudi Balling
Mar 14, 2013·Experimental Neurology·Ezia GuatteoJanusz Lipski
May 18, 2019·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Georg C ZieglerKlaus-Peter Lesch

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