The Journal of Neurophysiology Vol. 83 No. 2 February 2000, pp. 1010-1018
Copyright ©2000 by the American Physiological Society

Altered Regulation of Potassium and Calcium Channels by GABA_B and Adenosine Receptors in Hippocampal Neurons From Mice Lacking G_o

 ¹Department of Neurobiology, Harvard Medical School; and  ²Department of Cardiology, Brigham and Women's Hospital, Boston, Massachusetts 02115

Greif, Gabriela J., Deborah L. Sodickson, Bruce P. Bean, Eva J. Neer, and Ulrike Mende. Altered Regulation of Potassium and Calcium Channels by GABA_B and Adenosine Receptors in Hippocampal Neurons From Mice Lacking G_o. J. Neurophysiol. 83: 1010-1018, 2000. To examine the role of G_o in modulation of ion channels by neurotransmitter receptors, we characterized modulation of ionic currents in hippocampal CA3 neurons from mice lacking both isoforms of G_o. In CA3 neurons from G_o^/ mice, 2-chloro-adenosine and the GABA_B-receptor agonist baclofen activated inwardly rectifying K⁺ currents and inhibited voltage-dependent Ca²⁺ currents just as effectively as in G_o^+/+ littermates. However, the kinetics of transmitter action were dramatically altered in G_o^/ mice in that recovery on washout of agonist was much slower. For example, recovery from 2-chloro-adenosine inhibition of calcium current was more than fourfold slower in neurons from G_o^/ mice [time constant of 12.0 ± 0.8 (SE) s] than in neurons from G_o^+/+ mice (time constant of 2.6 ± 0.2 s). Recovery from baclofen effects was affected similarly. In neurons from control mice, effects of both baclofen and 2-chloro-adenosine on Ca²⁺ currents and K⁺ currents were abolished by brief exposure to external N-ethyl-maleimide (NEM). In neurons lacking G_o, some inhibition of Ca²⁺ currents by baclofen remained after NEM treatment, whereas baclofen activation of K⁺ currents and both effects of 2-chloro-adenosine were abolished. These results show that modulation of Ca²⁺ and K⁺ currents by G protein-coupled receptors in hippocampal neurons does not have an absolute requirement for G_o. However, modulation is changed in the absence of G_o in having much slower recovery kinetics. A likely possibility is that the very abundant G_o is normally used but, when absent, can readily be replaced by G proteins with different properties.