In guinea pig cardiac myocytes quinidine (20 ,uM) caused <10% tonic block reduction of the sodium current at -120 mV, but a fast pulse train reduced it more than 90%. Recovery from use-dependent block was time and voltage dependent, and was always slow (-r=34+10 seconds at -160 mV; r=90-'-35 seconds at -120 mV; n=15, mean+SD, p<0.001, paired t test). However, in association with repeated activa...

Retinal bipolar neurons transmit visual information by means of graded synaptic potentials that spread to the synaptic terminal without sodium-dependent action potentials. Although action potentials are not involved, voltage-dependent sodium channels may enhance subthreshold depolarizing potentials in the dendrites and soma of bipolar cells, as they do in other CNS neurons. We report here that ...

BACKGROUND Voltage-gated sodium channels play key roles in acute and chronic pain processing. The molecular, biophysical, and pharmacological properties of sodium channel currents have been extensively studied for peripheral nociceptors while the properties of sodium channel currents in dorsal horn spinal cord neurons remain incompletely understood. Thus far, investigations into the roles of so...

KEY POINTS Sodium channels are critical for supporting fast action potentials in neurons; even mutations which cause small changes in sodium channel activity can have devastating consequences for the function of the nervous system. Alternative splicing also changes the activity of sodium channels, and while it is highly conserved, it is not known whether the functional role of this splicing is ...

Hypertension is a major risk factor for heart attacks, stroke, and kidney failure. It is estimated to cause as many as 25% of all deaths in the United States, particularly for African Americans, in whom the disease is both more common and more severe. Essential hypertension is a multifactorial disorder influenced by both genetic and environmental factors. Physiological studies have shown that t...

The modulated receptor hypothesis states that sodium channels have a specific receptor for antiarrhythmic drugs. Therefore, two agents that block sodium channels by binding to this receptor are expected to compete for occupancy. Glycylxylidide (GX) is a deethylated metabolite of lidocaine that accumulates in patients on lidocaine therapy. In single, voltage-clamped cardiocytes, GX, like lidocai...

The hormone aldosterone increases extracellular fluid volume and blood pressure by activating epithelial Na+ channels (ENaCs). Serum- and glucocorticoid-induced kinase 1 (SGK1) is an aldosterone-stimulated signaling molecule that enhances distal nephron Na+ transport, in part by preventing the internalization of ENaCs from the plasma membrane. In this issue of the JCI, Zhang et al. demonstrate ...

The state dependence of Na channel modification by the alkaloid neurotoxin veratridine was investigated with single-channel and whole-cell voltage-clamp recording in neuroblastoma cells. Several tests of whole-cell Na current behavior in the presence of veratridine supported the hypothesis that Na channels must be open in order to undergo modification by the neurotoxin. Modification was use dep...

RNA blot hybridization analyses using probes specific for sodium channels I, II and III revealed high levels of sodium channel I mRNA and low levels of sodium channel II and III mRNAs in peripheral nervous system (PNS) tissues. The developmental expression patterns of these mRNAs were generally similar to those described for the central nervous system. The small amounts of sodium channel I and ...