Effects of flecainide, a potent antiarrhythmic agent, on sodium channel availability was investigated in guinea pig single cardiac cells by the whole-cell voltage-clamp technique. Sodium current (INa) experiments were performed at 170 C, and maximum upstroke velocity (Vmax) experiments were performed at 370 C. Flecainide (3 ,M) caused little tonic block, but reduced sodium channel availability ...

Although it is well established that hyperexcitability andyor increased baseline sensitivity of primary sensory neurons can lead to abnormal burst activity associated with pain, the underlying molecular mechanisms are not fully understood. Early studies demonstrated that, after injury to their axons, neurons can display changes in excitability, suggesting increased sodium channel expression, an...

Amiloride-sensitive sodium channels are localized to the microvillar domain of apical membranes in sodium-transporting renal epithelial cells. To elucidate the elements that maintain sodium channel distribution at the apical membrane, we searched for specific proteins associating with the channel. Triton X-100 extraction of A6 epithelial cells reveals that sodium channels are associated with de...

The purified Na+ channel from rat brain consists of a (260 kDa), Bl (36 kDa), and ,192 (33 kDa) subunits. Pure ,t?l subunits were prepared from purified rat brain Na+ channels which had been adsorbed to hydroxylapatite resin and used to prepare specific anti-81 subunit antiserum. Antibodies purified from this antiserum by antigen affinity chromatography immunoprecipitate 12SI-labeled, purified ...

Voltage-gated sodium channels initiate action potentials in nerve, muscle, and other electrically excitable cells. Voltage-gated calcium channels are activated by depolarization during action potentials, and calcium influx through them is the key second messenger of electrical signaling, initiating secretion, contraction, neurotransmission, gene transcription, and many other intracellular proce...

We compared the maximal upstroke velocity of action potentials in short rabbit Purkinje fibers with sodium currents measured with a two-microelectrode voltage clamp. The number of sodium channels available to open during a sudden depolarization was varied either by blockade with tetrodotoxin or by inactivation with steady depolarizations. In both cases, the maximal upstroke velocity was found t...

We study how functional constraints bound and shape evolution through an analysis of mammalian voltage-gated sodium channels. The primary function of sodium channels is to allow the propagation of action potentials. Since Hodgkin and Huxley, mathematical models have suggested that sodium channel properties need to be tightly constrained for an action potential to propagate. There are nine mamma...

Voltage-gated sodium channels are responsible for action potential initiation and propagation in neurons, and modulation of their function has an important impact on neuronal excitability. Sodium channels are regulated by a Src-family tyrosine kinase pathway, and this modulation can be reversed by specifically bound receptor phosphoprotein tyrosine phosphatase-beta. However, the specific tyrosi...

Some strains of Heliothis virescens carry a novel sodium channel mutation, corresponding to the replacement of Val410 by Met (designated V410M) in the house fly Vssc1 sodium channel, that is genetically and physiologically associated with pyrethroid resistance. To test the functional significance of this mutation, we created a house fly Vssc1 sodium channel containing the V410M mutation by site...

1. Sodium channels mediate fast depolarization and conduct electrical impulses throughout nerve, muscle and heart. This paper reviews the links between sodium channel structure and function. 2. Sodium channels have a modular architecture, with distinct regions for the pore and the gates. The separation is far from absolute, however, with extensive interaction among the various parts of the chan...