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Bicuculline

A convulsant with synaptic and nonsynapticactions

Department of Neurology (Drs. Heyer and Macdonald) and Neurosciences Program (Dr. Nowak), University of Michigan Medical Center, Ann Arbor, MI.

Address correspondence and reprint requests to Dr. Macdonald, Neuroscience Laboratory Building, 1103 East Huron, Ann Arbor, MI 48109.

The convulsant bicuculline (BICUC) had both synaptic and nonsynaptic actions on mouse spinal cord neurons in primary dissociated cell culture. BICUC antagonized postsynaptic responses to the inhibitory neurotransmitter GABA (a synaptic action) and produced direct membrane depolarization by blocking a membrane potassium conductance and directly prolonging calcium-dependent action potentials (nonsynaptic actions). In cultured spinal cord neurons, BICUC also produced paroxysmal depolarizing events (PDE), which might be equivalent to in vivo convulsant-induced bursting in spinal cord neurons or paroxysmal depolarizing shifts (PDS) in cortical neurons. Thus, the concentrations of BICUC producing both synaptic and nonsynaptic actions overlapped those producing paroxysmal activity. The results suggest that in addition to antagonism of GABA-mediated synaptic inhibition, direct nonsynaptic actions of BICUC may be required for some neurons to develop PDS.

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