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In the present study, we characterized the intrinsic electrophysiological properties and the membrane currents activated by dopamine (DA) D2 and GABAB 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 GABAB 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-operatedwv G-protein-gated inwardly rectifying K+ channel 2 (GIRK2) might be related to the selective degeneration of the dopaminergic neurons. In addition, thewv 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.

The weaver Mutation Reverses the Function of Dopamine and GABA in Mouse Dopaminergic Neurons