Kvβ1.1 associates with Kvα1.4 in chinese hamster ovary cells and pigeon type II vestibular hair cells and enhances the amplitude, inactivation and negatively shifts the steady-state inactivation range

• Published in: Neuroscience 2008, Vol.152 (3), p.809-820
• Main Authors: Correia, M.J, Weng, T, Prusak, D, Wood, T.G
• Format: Article
• Language: English
• Subjects: A-type; alpha subunit; beta subunit; Biological and medical sciences; Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation; Fundamental and applied biological sciences. Psychology; inactivation; Motor control and motor pathways. Reflexes. Control centers of vegetative functions. Vestibular system and equilibration; Neurology; potassium channels; utricle; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.01.021

Abstract Although A-type potassium currents are found in type II hair cells in the inner ear of most species, the molecular mechanisms for activation and inactivation of the A-type potassium current (IA ) remain unknown. In frog semicircular canal hair cells, for example, there appear to be two classes of currents having either fast or slow inactivation [Norris CH, Ricci AJ, Housley GD, Guth PS (1992) The inactivating potassium currents of hair cells isolated from the crista ampullaris of the frog. J Neurophysiol 68:1642–1653; Russo G, Calzi D, Martini M, Rossi ML, Fesce R, Prigioni I (2007) Potassium currents in the hair cells of vestibular epithelium: position-dependent expression of two types of A channels. Eur J Neurosci 25:695–704]. It has been suggested that somehow the “ball and chain” mechanism (NH3 (N) terminus motif) is modified by alternative splicing to account for the two classes of inactivation. To examine other possibilities, we cloned alpha and beta subunits that comprise the A-type potassium channel complex in adult and embryonic pigeon brain, cochlea and labyrinth. By sequence homology, we concluded that the subunits present were Kvα1.4 and Kvβ1.1. The sequence of the open reading frame for Kvα1.4 contained the N-terminus, pore and COOH (C) terminus motifs for N-and C-type inactivation. The sequence for Kvβ1.1 displayed amino acids consistent with assembly and association with Kvα1.4 alpha subunits. Kvα1.4 and Kvβ1.1 were transfected either singly or in combination into Chinese hamster ovary (CHO) cells. These cells and native hair cells from the pigeon utricle were patch clamped and the inactivation properties of the A-type current were studied. In the native hair cells, the A-type current was identified by its pharmacological (4-aminopyridine (4-AP); IC50 =11 μM) and voltage dependent inactivation properties. A comparison of the mean time constants from best-fitted single exponential and sum of two exponential equations to the ionic current inactivation revealed the following. In CHO cells when Kvα1.4 was expressed alone, the mean time constant (τ1 =107 ms±19, N =32) was significantly ( P