In the present study, we characterized the intrinsic electrophysiological properties and the membrane currents activated by dopamine (DA) D2 and GABA (B) receptors in midbrain dopaminergic neurons, maintained in vitro in a slice preparation, from wild-type and homozygous weaver (wv/wv) mice. By using patch-clamp techniques, we found that membrane potential, apparent input resistance, and spontaneous firing of wv/wv dopaminergic neurons were similar to those of dopamine-containing cells recorded from nonaffected (+/+) animals. More interestingly, the wv/wv neurons were excited rather than inhibited by dopamine and the GABA(B) agonist baclofen. This neurotransmitter-mediated excitation was attributable to the activation of a G-protein-gated inward current that reversed polarity at a membrane potential of approximately -30 mV. We suggest that the altered behavior of the receptor-operated wv G-proteingated inwardly rectifying K+ channel 2 (GIRK2) might be related to the selective degeneration of the dopaminergic neurons. In addition, the wv GIRK2 would not only suppress the autoreceptor-mediated feedback inhibition of DA release but could also establish a feedforward mechanism of DA release in the terminal fields.
CITATION STYLE
Guatteo, E., Fusco, F. R., Giacomini, P., Bernardi, G., & Mercuri, N. B. (2000). The weaver mutation reverses the function of dopamine and GABA in mouse dopaminergic neurons. Journal of Neuroscience, 20(16), 6013–6020. https://doi.org/10.1523/jneurosci.20-16-06013.2000
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