Muscarinic receptors differentially modulate the persistent potassium current in striatal spiny projection neurons

Cholinergic regulation of striatal spiny projection neuron activity is pred ominantly mediated through muscarinic receptor modulation of several subcla sses of ion channels. Because of its critical role in governing the recurri ng episodes of hyperpolarization and depolarization characteristic of spiny neurons in vivo, the 4-aminopyridine-resistant, persistent potassium (K+) current, I-Krp. would be a strategic target for modulation The present resu lts shaw that I-Krp can be either suppressed or enhanced by muscarinic rece ptor stimulation. Biophysical analysis demonstrated that the depression of I-Krp was associated with a hyperpolarizing shift in the voltage dependence of inactivation and a reduction in maximal conductance. By contrast, the e nhancement of I-Krp was linked to hyperpolarizing shifts in both activation and inactivation voltage dependencies. Viewed in the context of the natura l activity of spiny neurons, muscarinic depression of I-Krp should uniforml y increase excitability in both hyperpolarized and depolarized states. In t he hyperpolarized state, the reduction in maximal conductance should bolste r the efficacy of impending excitatory input. Likewise, in the depolarized state, the decreased availability of I-Krp produced by the shift in inactiv ation should enhance ongoing synaptic input. The alterations associated wit h enhancement of I-Krp are predicted to have a more dynamic influence on sp iny cell excitability. In the hyperpolarized state, the negative shift in a ctivation should increase the Bow of I-Krp and attenuate subsequent excitat ory synpatic input; whereas once the cell has traversed into the depolarize d state, the negative shift in inactivation should reduce the availability of this current and diminish its influence on the existing excitatory barra ge.