K(V)1 and K(V)3 Potassium Channels Identified at Presynaptic Terminals of the Corticostriatal Synapses in Rat

In the last years it has been increasingly clear that K(V)-channel activity modulates neurotransmitter release. The subcellular localization and composition of potassium channels are crucial to understanding its influence on neurotransmitter release. To investigate the role of K(V) in corticostriatal synapses modulation, we combined extracellular recording of population-spike and pharmacological blockage with specific and nonspecific blockers to identify several families of K(V) channels. We induced paired-pulse facilitation (PPF) and studied the changes in paired-pulse ratio (PPR) before and after the addition of specific K(V) blockers to determine whether particular K(V) subtypes were located pre- or postsynaptically. Initially, the presence of K(V) channels was tested by exposing brain slices to tetraethylammonium or 4-aminopyridine; in both cases we observed a decrease in PPR that was dose dependent. Further experiments with tityustoxin, margatoxin, hongotoxin, agitoxin, dendrotoxin, and BDS-I toxins all rendered a reduction in PPR. In contrast heteropodatoxin and phrixotoxin had no effect. Our results reveal that corticostriatal presynaptic K(V) channels have a complex stoichiometry, including heterologous combinations K(V)1.1, K(V)1.2, K(V)1.3, and K(V)1.6 isoforms, as well as K(V)3.4, but not K(V)4 channels. The variety of K(V) channels offers a wide spectrum of possibilities to regulate neurotransmitter release, providing fine-tuning mechanisms to modulate synaptic strength.