Cell-type-specific splicing of KChIP4 mRNA correlates with slower kinetics of A-type current

Abstract

In neurons, rapidly inactivating A-type potassium currents regulate repetitive firing and sensitivity to synaptic inputs both in the soma and in the dendrites. It has been established that Kv4 family subunits with several modifying proteins such as KChIPs are responsible for A-type current in most neurons. However, it is not clear which of these modifying proteins are responsible for the observed difference in the properties of A-type currents in the neurons. For example, in globus pallidus (GP) and basal forebrain (BF) neurons in rats, A-type current possesses a slowly inactivating (tau > 80 ms) component of inactivation that is absent in the currents obtained from striatal cholinergic interneurons (StrI) and hippocampal area CA1 pyramidal neurons (HIP). It has been shown that KChIP4 splice variant A but not splice variant B can increase inactivation rates of Kv4 current to > 100 ms in Xenopus oocytes. We tested the hypothesis that cell-specific expression of KChIP4A is responsible for the slow inactivation of A-type current in these neurons. Employing single-cell RT-PCR in acutely dissociated rat neurons, KChIP4A mRNA was detected in 12/14 GP cells and in 12/14 BF neurons whereas it was not detected in any StrI or HIP cells. By contrast, the KChIP4 splice variant B was detected in all four types of cells. Moreover, deactivation rates at -100 mV were slower in BF and GP cells than in StrI and HIP neurons as expected, owing to the presence KChIP4A in BF and GP neurons. These data are consistent with our initial hypothesis.