Highly purified sodium channel protein from the electric eel, Electrophorus electricus, was reconstituted into liposomes and incorporated into planar bilayers made from neutral phospholipids dissolved in decane. The purest sodium channel preparations consisted of only the large, 260-kD tetrodotoxin (TTX)-binding polypeptide. For all preparations, batrachotoxin (BTX) induced long-lived single-ch...

Deoxycholate can react with sodium channels with a high potency. The apparent dissociation constant for the saturable binding reaction is 2 microM at 8 degrees C, and the heat of reaction is approximately -7 kcal/mol. Four independent test with Na-free media, K-free media, tetrodotoxin, and pancuronium unequivocally indicate that it is the sodium channel that is affected by deoxycholate. Upon d...

The sodium channel of the excitability mechanism in nerve membranes is about as permeable to hydroxylamine and hydrazine cations as it is to sodium ions. It is impermeable to methylamine cations. This selectivity is explained by supposing that an oxygen group in the channel must receive a hydrogen bond from the permeating cation at the same time as the cation lies against another negatively cha...

Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Na(v)1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe ca...

Voltage-gated sodium channels are known to play a pivotal role in perception and transmission of pain sensations. Gain-of-function mutations in the genes encoding the peripheral neuronal sodium channels, hNav1.7-1.9, cause human painful diseases. Thus while treatment of chronic pain remains an unmet clinical need, sodium channel blockers are considered as promising druggable targets. In a previ...

introduction: neurons in layer ii and iii of the somatosensory cortex in rats show high frequency (33 ± 13 hz) of miniature excitatory postsynaptic currents (mepscs) that their rates and amplitudes are independent of sodium channels. there are some changes in these currents in neurodegenerative and psychological disorders. regarding to well known roles of the neuromodulatory brain systems in th...

This paper proposes a new double-chamber model (DCM) of ion channels. The model ion channel consists of a series of three pores alternating with two chambers. The chambers are net negatively charged. The chamber's electric charge originates from dissociated amino acid side chains and is pH dependent. The chamber's net negative charge is compensated by cations present inside the chamber and in a...

Single sodium channels from human brain cortex tissue were incorporated into voltage-clamped planar lipid bilayers in the presence of batrachotoxin and studied with various doses of the new anaesthetic compound propofol (2,6-diisopropylphenol). Propofol was found to depress two major sodium channel functions, leading to a reduction of the time-averaged fractional channel open-time (half-maximal...