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Inwardly rectifying potassium channels are important in cellular repolarization of many excitable tissues. Amino acid sequence alignment of different mammalian inward rectifier K(+) channels revealed two absolutely conserved cysteine residues in the putative extracellular face, suggesting a possible disulfide bond. Replacement of these cysteine residues in(More)
The aim of the present study was to compare the biophysical properties and Cd2+ sensitivity of Kv4.2 and Kv1.4 in Xenopus oocytes with those of native transient outward potassium currents in rat and rabbit ventricular myocytes. In Xenopus oocytes, Kv4.2 inactivated at hyperpolarized voltages (V(1/2)inact = -58.4 +/- 0.96 mV, n = 12) and recovered from(More)
Voltage-gated Na(+) (Na(v)) channels are responsible for initiating action potentials in excitable cells and are the targets of local anesthetics (LA). The LA receptor is localized to the cytoplasmic pore mouth formed by the S6 segments from all four domains (DI-DIV) but several outer pore-lining residues have also been shown to influence LA block (albeit(More)
Heart failure is the leading cause of mortality in patients with transfusional iron (Fe) overload in which myocardial iron uptake ensues via a transferrin-independent process. We examined the ability of L-type Ca2+ channel modifiers to alter Fe2+ uptake by isolated rat hearts and ventricular myocytes. Perfusion of rat hearts with 100 nmol/L 59Fe2+ and 5(More)
Voltage-gated K(+) (Kv) 2.1 is the dominant Kv channel that controls membrane repolarization in rat islet beta-cells and downstream insulin exocytosis. We recently showed that exocytotic SNARE protein SNAP-25 directly binds and modulates rat islet beta-cell Kv 2.1 channel protein at the cytoplasmic N terminus. We now show that SNARE protein syntaxin 1A(More)
Replacement of individual P-loop residues with cysteines in rat skeletal muscle Na+ channels (SkM1) caused an increased sensitivity to current blockade by Cd2+ thus allowing detection of residues lining the pore. Simultaneous replacement of two residues in distinct P-loops created channels with enhanced and reduced sensitivity to Cd2+ block relative to the(More)
We have examined the effects of a beta-scorpion toxin purified from the venom of the Venezuelan scorpion Tityus discrepans, TdVIII, on heterologously expressed rat skeletal muscle Na+ channels (rSkM1). TdVIII (100 nM) produced a leftward shift in the voltage dependence of activation and reduced the peak Na+ conductance of rSkM1 channels coexpressed with the(More)
To explore the role of pore-lining amino acids in Na+ channel ion-selectivity, pore residues were replaced serially with cysteine in cloned rat skeletal muscle Na+ channels. Ionic selectivity was determined by measuring permeability and ionic current ratios of whole-cell currents in Xenopus oocytes. The rSkM1 channels displayed an ionic selectivity sequence(More)
Local anesthetics inhibit Na+ channels in a variety of tissues, leading to potentially serious side effects when used clinically. We have created a series of novel local anesthetics by connecting benzocaine (BZ) to the sulfhydryl-reactive group methanethiosulfonate (MTS) via variable-length polyethylether linkers (L) (MTS-LX-BZ [X represents 0, 3, 6, or(More)
Action potential prolongation is a common finding in human heart failure and in animal models of cardiac hypertrophy. The mechanism of action potential prolongation involves altered expression of a variety of depolarising and hyperpolarising currents in the myocardium. In particular, decreased density of the transient outward potassium current seems to play(More)