Sodium channels are expressed at high density in myelinated axons and play an obligatory role in conducting action potentials along axons within the mammalian brain and spinal cord. It is not surprising, therefore, that they are involved in several aspects of the pathophysiology of multiple sclerosis (MS). First, the deployment of additional sodium channels to demyelinated parts of the axon (wh...

Goniopora toxin (GPT), a polypeptide toxin of 9700 Da isolated from coral, markedly slows inactivation of sodium currents recorded under voltage clamp in mouse neuroblastoma cells. The voltage dependence of sodium channel activation is shifted to more negative membrane potentials by 9.8 +/- 2.1 mV, and the voltage dependence of channel inactivation is shifted to more positive membrane potential...

Pain resulting from chronic nerve injury or damage (so-called neuropathic pain) is a common and debilitating condition. Many studies indicate that tetrodotoxinresistant (TTX-R) sodium channels are highly expressed in nociceptors, the sensory neurons that mediate pain. It has also been suggested that a reduction in TTX-R expression or function reduces pain. Similarly, because axonal injury cause...

Introduction: Hydrogen sulfide (H2S) plays a key role in the regulation of vascular tone and protection of blood vessels against endothelial dysfunction. Since the mechanism of salt impairing H2S-induced vascular relaxation is not fully clear, therefore this study was designed to investigate the role of potassium (K+) channels in the vasodilatory effects of exogenous H2S in rat aortic rings.&nb...

Brilliant blue G (BBG), best known as an antagonist of P2X7 receptors, was found to inhibit voltage-gated sodium currents in N1E-115 neuroblastoma cells. Sodium currents elicited from a holding potential of -60 mV were blocked with an IC(50) of 2 μM. Block was enhanced in a use-dependent manner at higher stimulation rates. The voltage-dependence of inactivation was shifted in the hyperpolarizin...

Among proteins involved in neurological disease ion channels are amenable to the most detailed characterisation: patch-clamp methods allow the opening and closing of individual channels to be documented at millisecond resolution in response to precisely delivered stimuli (whether electrical or pharmacological). In theory, therefore, inherited disorders of ion channels should be ideal candidates...

We have previously presented evidence that electrical activity and increased cytosolic calcium reduce the density of sarcolemmal tetrodotoxin (TTX)-sensitive sodium channels in cultured rat muscle cells (Sherman, S. J., and W. A. Catterall (1984) Proc. Natl. Acad. Sci. U. S. A. 81: 262-266). We show here that growth of cells in ryanodine has a biphasic effect on sodium channel number. At low co...

Ionic currents through fast sodium channels in the neuronal somatic membrane were measured under voltage clamp conditions using external solutions of normal and low pH. Voltage-dependent inhibition of ionic currents through open channels was observed in acidic solutions. The voltage-dependent block of sodium channels may be explained by the presence of two acid groups at the channel. The parame...

W ithout voltage-gated sodium channels, heart muscle cells can’t keep a beat. Lowe et al. show how these cells, known as cardiomyocytes, direct channels to the right domain of their plasma membrane. Opening Nav1.5 sodium channels allows an inrush of sodium ions that depolarizes a cardiomyocyte. Patients who carry a faulty version of the channel are at risk for potentially lethal heart arrhythmi...