Ionic blockade of the rat connexin40 gap junction channel by large tetraalkylammonium ions Article

Musa, H, Gough, JD, Lees, WJ et al. (2001). Ionic blockade of the rat connexin40 gap junction channel by large tetraalkylammonium ions . 81(6), 3253-3274. 10.1016/S0006-3495(01)75960-7



cited authors

  • Musa, H; Gough, JD; Lees, WJ; Veenstra, RD

fiu authors

abstract

  • The rat connexin40 gap junction channel is permeable to monovalent cations including tetramethylammonium and tetraethyiammonium ions. Larger tetraalkyammonium (TAA+) ions beginning with tetrabutylammonium (TBA+) reduced KCI junctional currents disproportionately. Ionic blockade by tetrapentylammonium (TPeA+) and tetrahexylammonium (THxA+) ions were concentration- and voltage-dependent and occurred only when TAA+ ions were on the same side as net K+ efflux across the junction, indicative of block of the ionic permeation pathway. The voltage-dependent dissociation constants (Km(Vj)) were lower for THxA+ than TPeA+, consistent with steric effects within the pore. The Km-Vj relationships for TPeA+ and THxA+ were fit with different reaction rate models for a symmetrical (homotypic) connexin gap junction channel and were described by either a one- or two-site model that assumed each ion traversed the entire Vj field. Bilateral addition of TPeA+ ions confirmed a common site of interaction within the pore that possessed identical Km(Vj) values for cis-trans concentrations of TPeA+ ions as indicated by the modeled I-V relations and rapid channel block that precluded unitary current measurements. The TAA+ block of K+ currents and bilateral TPeA+ interactions did not alter Vj-gating of Cx40 gap junctions. N-octyl-tributylammonium and -triethylammonium also blocked rCx40 channels with higher affinity and faster kinetics than TBA+ or TPeA+, indicative of a hydrophobic site within the pore near the site of block.

publication date

  • January 1, 2001

Digital Object Identifier (DOI)

start page

  • 3253

end page

  • 3274

volume

  • 81

issue

  • 6