Regulation of action potential size and excitability in substantia nigra compacta neurons: sensitivity to...

Slow, pacemaker-like firing is due to intrinsic membrane properties in substantia nigra compacta (SNc) neurons in vitro. How these properties interact with afferent synaptic inputs is not fully understood. In this study, intracellular recordings from SNc neurons in brain slices showed that spontaneous action potentials (APs) were attenuated when generated from lower than normal threshold. Such APs were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and could be related to non-N-methyl-D-aspartate (NMDA) receptor-mediated spontaneous excitatory postsynaptic potentials (EPSPs). The AP attenuation was reproduced by stimulus-evoked EPSPs and by current injections to the soma. APs evoked from holding potentials between -40 and -60 mV were reduced in width by Cd(2+) (0. 2 mM). Tetraethylammonium chloride (TEA, 10 mM) or 4-aminopyridine (4-AP, 5 mM) increased the AP width. However, at more negative holding potentials, Cd(2+) and TEA were inefficacious, whereas 4-AP enlarged the AP, partly via induction of a Cd(2+)-sensitive component. A monophasic afterhyperpolarization (AHP), following attenuated APs, was little affected by either Cd(2+) or TEA, but inhibited by 4-AP, which induced an additional, slow component, sensitive to Cd(2+) or apamin (100 nM). The AP delay showed a discontinuous relation to the amplitude or slope of the injected current (delay shift), which was sensitive to low doses of 4-AP (0. 05 mM). The initial time window before the delay shift was longer than the rise time of EPSPs. It is suggested that a 4-AP-sensitive current prevents or postpones discharge during slow depolarization's, but allows direct excitation by fast EPSPs. Fast excitation leads to AP attenuation, primarily due to strong activation of 4-AP-sensitive current. This seems to cause inhibition of the Ca(2+) current during the AP and reduction of Ca(2+)-dependent K(+) currents. Together, these properties are likely to influence the excitability and the local, somatodendritic effects of the AP, in a manner that discriminates between firing induced by the intrinsic pacemaker mechanism and fast synaptic potentials.