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J Neurophysiol 81: 1318-1329, 1999;
0022-3077/99 $5.00
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The Journal of Neurophysiology Vol. 81 No. 3 March 1999, pp. 1318-1329
Copyright ©1999 by the American Physiological Society

Interactive Effects of the GABABergic Modulation of Calcium Channels and Calcium-Dependent Potassium Channels in Lamprey

Jesper Tegnér1,2 and Sten Grillner1

 1Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm; and  2Studies of Artificial Neural Systems, Department of Numerical Analysis and Computing Science, Royal Institute of Technology, S-100 44 Stockholm, Sweden

Tegnér, Jesper and Sten Grillner. Interactive effects of the GABABergic modulation of calcium channels and calcium-dependent potassium channels in lamprey. The GABAB-mediated modulation of spinal neurons in the lamprey is investigated in this study. Activation of GABAB receptors reduces calcium currents through both low- (LVA) and high-voltage activated (HVA) calcium channels, which subsequently results in the reduction of the calcium-dependent potassium (KCa) current. This in turn will reduce the peak amplitude of the afterhyperpolarization (AHP). We used the modulatory effects of GABAB receptor activation on N-methyl-D-aspartate (NMDA)-induced, TTX-resistant membrane potential oscillations as an experimental model in which to separate the effects of GABAB receptor activation on LVA calcium channels from that on KCa channels. We show experimentally and by using simulations that a direct effect on LVA calcium channels can account for the effects of GABAB receptor activation on intrinsic membrane potential oscillations to a larger extent than indirect effects mediated via KCa channels. Furthermore, by conducting experiments and simulations on intrinsic membrane potential oscillations, we find that KCa channels may be activated by calcium entering through LVA calcium channels, providing that the decay kinetics of the calcium that enters through LVA calcium channels is not as slow as the calcium entering via NMDA receptors. A combined experimental and computational analysis revealed that the LVA calcium current also contributes to neuronal firing properties.




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