Increasing the hydrogen ion concentration of the bathing medium reversibly depresses the sodium permeability of voltage-clamped frog nerves. The depression depends on membrane voltage: changing from pH 7 to pH 5 causes a 60% reduction in sodium permeability at +20 mV, but only a 20% reduction at +180 mV. This voltage-dependent block of sodium channels by hydrogen ions is explained by assuming t...

We used the patch clamp technique to study the nature of the late sodium current in guinea pig ventricular myocytes. In a cell attached mode of single channel recording at room temperature (22-24 degrees C) two kinds of late (100 msec or more after beginning of the depolarizing pulse) sodium channel activities were recognized. One is isolated brief openings appearing once for about 120 depolari...

Norepinephrine and carbamoylcholine stimulate accumulation of [3H]inositol phosphates from [3H]inositol-labeled guinea pig cerebral cortical synaptoneurosomes through interaction with alpha 1-adrenergic and muscarinic receptors, respectively. In addition to such agonist, a variety of natural products that affect voltage-dependent sodium channels can markedly stimulate accumulation of [3H]inosit...

In vivo, the enzyme 11 -hydroxysteroid dehydrogenase type 2 influences ligand access to the mineralocorticoid receptor. Ablation of the encoding gene, HSD11B2, causes the hypertensive syndrome of apparent mineralocorticoid excess. Studies in humans and experimental animals have linked reduced 11 -hydroxysteroid dehydrogenase type 2 activity and salt sensitivity of blood pressure. In the present...

In vivo, the enzyme 11β-hydroxysteroid dehydrogenase type 2 influences ligand access to the mineralocorticoid receptor. Ablation of the encoding gene, HSD11B2, causes the hypertensive syndrome of apparent mineralocorticoid excess. Studies in humans and experimental animals have linked reduced 11β-hydroxysteroid dehydrogenase type 2 activity and salt sensitivity of blood pressure. In the present...

Antibodies were raised against a synthetic peptide corresponding to residues 927-938 of the eel electroplax sodium channel primary sequence. This segment, lying between putative internal repeat domains II and III, is postulated to be exposed on the cytoplasmic surface of the membrane in several recent models of channel tertiary structure and on the external surface in another. The antiserum and...

Voltage-clamp experiments on isolated giant axons of the cockroach Periplaneta americana L. show that chemically synthesized saxitoxin specifically and reversibly blocks the transient inward sodium current without affecting the steady-state outward potassium current. From the concentration depending of sodium current suppression it is concluded that individual sodium channels are blocked by sin...

The pathomechanism of familial hypokalemic periodic paralysis (HypoPP) is a mystery, despite knowledge of the underlying dominant point mutations in the dihydropyridine receptor (DHPR) voltage sensor. In five HypoPP families without DHPR gene defects, we identified two mutations, Arg-672-->His and -->Gly, in the voltage sensor of domain 2 of a different protein: the skeletal muscle sodium chann...

The Drosophila para sodium channel a subunit was expressed in Xenopus oocytes alone and in combination with tipE , a putative Drosophila sodium channel accessory subunit. Coexpression of tipE with para results in elevated levels of sodium currents and accelerated current decay. Para/TipE sodium channels have biophysical and pharmacological properties similar to those of native channels. However...