Properties of voltage-gated K+ currents expressed inXenopus oocytes by mKv1.1, mKv1.2 and their heteromultimers as revealed by mutagenesis of the dendrotoxin-binding site in mKv1.1

Abstract

Two similar mouse Shaker-like K+ channel genes, mKv1.1 and mKv1.2, have been shown to form heteromultimers in vivo. The predicted amino acid sequence of each channel is nearly identical in mice, rats and humans, suggesting that each has been highly conserved evolutionarily. Here we report the biophysical and pharmacological properties of each channel when expressed alone or when coexpressed in Xenopus oocytes. The voltage sensitivities of activation were similar for both, but the voltages at which the K+ conductances were half-maximal (V1/2) were -37 mV and -27 mV for mKv1.1 and mKv1.2 respectively. Both displayed voltage-dependent, but incomplete, inactivation following a prepulse with mKv1.2 showing the greater degree of inactivation. For mKv1.1, the onset and recovery from inactivation could be described by single, slow time constants (2-4 s), whereas for mKv1.2 the onset and recovery from inactivation displayed a second, faster time constant (< 400 ms). Using a mutant mKv1.1 that is 100-fold less sensitive to dendrotoxin-I than mKv1.1, we demonstrate that this mutant mKv1.1 and wild-type mKv1.2 subunits can form heteromultimeric channels. With some exceptions, of unknown significance, the biophysical properties of the heteromultimeric channels formed by wild-type mKv1.1 and mKv1.2 subunits were intermediate between those of mKv1.1 and mKv1.2 homomultimers, but quantitatively more similar to the more abundant subunit.

Unmasking of Spiral Ganglion Neuron Firing Dynamics by Membrane Potential and Neurotrophin-3

“…Although we focused here on K v 1.1 protein expression, we previously examined K v 1.2 channels, which have a similar expression profile as K v 1.1 (Liu et al, 2014). Further, the K v 1 family of channels are known to form heteromeric and homomeric complexes with differing properties (Ruppersberg et al, 1990;Hopkins et al, 1994), thus adding to the complexity of excitability available to spiral ganglion neurons. Hypothetically, however, a mechanism as simple as depolarization-induced K v 1 inactivation (Dodson et al, 2002) can have a profound effect on the transition to different accommodation classes that would essentially provide instantaneous, yet reversible, regulatory control.…”

Common Sensory Inputs and Differential Excitability of Segmentally Homologous Reticulospinal Neurons in the Hindbrain

“…DTX-I is a selective blocker of potassium channels that contain mammalian Kv1.1, Kv1.2, or Kv.1.6 ␣-subunits (Hopkins et al, 1994;Harvey, 1997). Little is known about the molecular structure and tissue expression of potassium channels in the fish brain.…”

“…Because voltagegated potassium channels containing a Kv1.2 ␣-subunit are sensitive to DTX-I (Hopkins et al, 1994;Harvey, 2001), we investigated the expression of the Kv1.2 ␣-subunit in the goldfish hindbrain with immunohistochemistry. As shown in Figure 10, the soma and dendrites of M-cells were immunoreactive to the anti-Kv1.2 antibody (Fig.…”

“…We first assessed the involvement of the DTX-sensitive potassium conductance, which has been shown to contribute to single spiking in central auditory neurons of mammals and birds (Brew and Forsythe, 1995;Rathouz and Trussell, 1998;Bal and Oertel, 2001;Dodson et al, 2002). DTX is a selective blocker of voltage-gated potassium channels composed of subunits from the Kv1 family (Hopkins et al, 1994;Harvey, 1997Harvey, , 2001). During application of DTX-I (1 M) to the brain surface, depolarization of the M-cell resulted in repetitive firing at frequencies increased with the amplitude of the injected current (Fig.…”

Tonotopic Gradients of Membrane and Synaptic Properties for Neurons of the Chicken Nucleus Magnocellularis

“…Channels of Kv1.1, Kv1.2, and Kv1.6 are blocked by DTX (Hopkins et al, 1994;Harvey, 2001). Among these channels, Kv1.1 expression showed gradients systematically along the tonotopic axis (Figs.…”