Kinetics of two voltage-gated K+ conductances in substantia nigra dopaminergic neurons

The substantia nigra (SN) is part of the basal ganglia which is a section in the movement circuit in the brain. Dopaminergic neurons (DA) constitute the bulk of substantia nigra neurons and are related to diseases such as Parkinson's disease. Aiming at describing the mechanism of action potential firing in these cells, the current research examined the biophysical characteristics of voltage-gated K+ conductances in the dopaminergic neurons of the SN. The outside-out configuration of the patch-clamp technique was used to measure from dopaminergic neurons in acute brain slices. Two types of K+ voltage-gated conductances, a fast-inactivating A-type-like K+ conductance (K(fast)) and a slow-inactivating delayed rectifier-like K+ conductance (K(slow)), were isolated in these neurons using kinetic separation protocols. The data suggested that a fast-inactivating conductance was due to 69% of the total voltage-gated K+ conductances, while the remainder of the voltage-gated K+ conductance was due to the activation of a slow-inactivating K+ conductance. The two voltage-gated K+ conductances were analyzed assuming a Hodgkin-Huxley model with two activation and one inactivation gate. The kinetic models obtained from this analysis were used in a numerical simulation of the action potential. This simulation suggested that K(fast) may be involved in the modulation of the height and width of action potentials initiated at different resting membrane potentials while K(slow) may participate in action potential repolarization. This mechanism may indicate that SN dopaminergic neurons may perform analog coding by modulation of action potential shape.