Healthy cerebrovascular myocytes express members of several different ion channel families which regulate resting membrane potential, vascular diameter, and vascular tone and are involved in cerebral autoregulation. In animal models, in response to subarachnoid blood, a dynamic transition of ion channel expression and function is initiated, with acute and long-term effects differing from each o...

KCNQ potassium channels are activated by changes in transmembrane voltage and play an important role in controlling electrical excitability. Human mutations of KCNQ2 and KCNQ3 potassium channel genes result in reduction or loss of channel activity and cause benign familial neonatal convulsions (BFNCs). Thus, small molecules capable of augmenting KCNQ currents are essential both for understandin...

The cystic fibrosis transmembrane conductance regulator (CFTR) protein has the ability to function as both a chloride channel and a channel regulator. The loss of these functions explains many of the manifestations of the cystic fibrosis disease (CF), including lung and pancreatic failure, meconium ileus, and male infertility. CFTR has previously been implicated in the cell regulatory volume de...

Three-dimensional Brownian dynamics simulations are used to study conductance of the KcsA potassium channel using the known crystallographic structure. Employing an open-state channel created by molecular dynamics simulations, current-voltage and current-concentration curves broadly consistent with experimental measurements are obtained. In the absence of an applied potential, the channel house...

The majority of the polytopic proteins that are synthesized at the ER (endoplasmic reticulum) are integrated co-translationally via the Sec61 translocon, which provides lateral access for their hydrophobic TMs (transmembrane regions) to the phospholipid bilayer. A prolonged association between TMs of the potassium channel subunit, TASK-1 [TWIK (tandem-pore weak inwardly rectifying potassium cha...

The Kv3.1 channel subunit, when expressed heterologously, gives rise to a high-threshold noninactivating potassium current. Experiments with auditory neurons have suggested that the presence of this channel subunit enables them to fire action potentials at high frequencies. We have found that the expression levels of Kv3.1 transcripts increase in inferior colliculus neurons before the onset of ...

Axons degenerate after injury and in neuropathies and disease via a self-destruction program whose mechanism is poorly understood. Axons that have lost connection to their cell bodies have altered electrical and synaptic activities, but whether such changes play a role in the axonal degeneration process is not clear. We have used a Drosophila model to study the Wallerian degeneration of motoneu...

Opening of potassium channels on vascular smooth muscle cells with resultant hyperpolarization plays a central role in several mechanisms of vasodilation. For example, in the arteriolar circulation where tissue perfusion is regulated, there is an endothelial derived hyperpolarizing factor that opens vascular smooth muscle calcium-activated potassium channels, eliciting dilation. Metabolic vasod...

The present study reports a microwave-assisted method for the synthesis of twelve novel tricyclic 1,4-dihydropyridine derivatives in which dimethyl-substituted cyclohexane and / or tetrahydrothiophene rings are fused to the DHP ring. The structures of the compounds were confirmed by spectral methods and elemental analysis. The potassium channel opening effects of the compounds were determined o...

Neuronal differentiation often proceeds differently in vitro than it does in vivo. Previous work demonstrated that overexpression of potassium channel RNA reduces the number of morphologically identifiable neurons that appear in cultures prepared from neural plate stage (17-1/2 hr) embryos (Jones and Ribera, 1994). Here, we report that morphological differentiation of neurons in situ is only sl...