Cholinergic and Dopaminergic Modulation of Potassium Conductances in Neostriatal Neurons

Muscarinic and dopaminergic ligands exert their principal effects on excitability by modulating voltage-dependent conductances. Potassium currents activated by depolarization are among the conductances modulated. These currents can be divided into rapidly (Af) and slowly inactivating (A(s)) A-currents and a delayed rectifier current. The voltage-dependence and maximal conductance of the Af current are modulated by muscarinic agonists, presumably through a M1 receptor. This pharmacological class of receptors is coupled to phosphoinositide hydrolysis as well as the inhibition of cAMP accumulation. The nature of the muscarinic modulation of the Af current suggests that acetylcholine should not be viewed as excitatory or inhibitory but rather as enhancing state stability. Dopaminergic agonists appear to selectively modulate the A(s) current, rather than the Af current. This current is expressed late in the postnatal development of neostriatal neurons and plays an important part in regulating integrative behavior. Both D1 and D2 receptors mediate dopaminergic modulation. D1 agonists suppress this current whereas D2 agonists enhance it. The interaction of the dopaminergic modulation with the state transitions medium spiny neurons undergo in generating spike activity has yet to be fully explored. Nevertheless, it is clear that the modulation of the A(s) current provides a basis on which dopamine might interact with acetylcholine in controlling neostriatal excitability.