Subtypes of substantia nigra dopaminergic neurons revealed by apamin: Autoradiographic and electrophysiological studies

In the intact animal, some substantia nigra dopaminergic neurons exhibit regular and some exhibit burst firing patterns. In the in vitro slice preparation, however, all dopaminergic neurons exhibit a nonburst firing pattern. Burst firing patterns are thought to be regulated, in part, by a small conductance calcium-activated potassium channel (SK channels). To test whether SK channels reside within the midbrain dopaminergic cell regions of the mouse, receptor autoradiographic experiments were conducted with the SK channel antagonist, ¹²⁵I-apamin. To determine whether SK channels play a role in burst firing pattern generation in substantia nigra dopaminergic neurons, changes in firing patterns of these cells were examined in the in vitro slice preparation following apamin superfusion (1-1000 nM). It was demonstrated that a) specific binding of radiolabeled apamin was found within the dopaminergic cell regions of the substantia nigra pars compacta and ventral tegmental area (2.7-4.7 fmol/mg tissue): b) the firing patterns of less than half of the dopaminergic neurons were changed from a regular pattern to that of a burster with concentrations as low as I nM, but the firing patterns of many neurons were not changed by the drug; and c) blockade of the SK channel did not interfere with the inhibitory effects of dopamine on dopaminergic neuronal impulse flow, indicating that the known hyperpolarizing effects mediated by this dopamine receptor are not importantly mediated via the SK channel.