Barbiturate depression of a K⁺ dependent inhibitory synapse is independent of dendritic cable filtering

Summary

Technical limitations with intracellular electrophysiological methods usually restrict recording of postsynaptic potentials only from neuronal soma, a site remote from the actual synapse. The intervening dendritic cable interposed between the actual synapse and the site of recording can significantly filter the synaptic signal. Therefore, investigations of drug effect on synaptic mechanisms, based on postsynaptic recordings obtained at the soma, must be interpreted with care. The potential role of dendritic cable filtering in the atypical pentobarbital depression of a K⁺-dependent inhibitory synapse between the P to Nut cell in the posterior packet of the leech was investigated. The effective electrical geometry under the conditions of control and 0.5 mM PNB sufficient to completely abolish the postsynaptic potential were determined from analyses of the membrane charging curves assuming the lumped-soma-short-cable model. Under the control condition, the postsynaptic Nut cell exhibits dendritic dominance with rho = 2.52, normalized equivalent cable length l= 1.08, and a membrane time constant tau_o=52 ms. With phenobarbital application, changes in the geometrical parameters consistent with a decrease in the specific membrane resistance R_m are observed. Simulation of the drug induced change in the electrical geometry demonstrates that the decrease in the post synaptic potential is largely due to the decrease in the soma input resistance and an increase in the cable filter contributes little to the observed depression of the postsynaptic potential. However, the combined effect of the decrease in the input resistance and the increase in the cable filtering of synaptic current is insufficient in explaining the observed total block of the synaptic potential by PNB. Therefore, in leech, PNB block of a K⁺-dependent inhibitory synapse is not an epiphenomenon due to altered cable filtering.