Current Pharmaceutical Design - Volume 11, Issue 21, 2005

Local anesthetic drugs interfere with excitation and conduction by action potentials in the nervous system and in the heart by blockade of the voltage-gated Na channel. Drug affinity varies with gating state of the channel. The drugs show low affinity at slow excitation rates, but high affinity when the channels are opened and inactivated during action potentials at high frequency, as they are during pain or during a cardiac ar Read More

TRPV1 is a channel expressed highly in small sensory neurons. TRPV1 is a ligand-gated, cation channel that is activated by heat, acid and capsaicin, a principal ingredient in hot peppers. Because of its possible role as a polymodal molecular detector, TRPV1 is studied most extensively. In mice lacking TRPV1, thermal hyperalgesia induced by inflammation is reduced, suggesting a role for mediating inflammatory pain. Activity of Read More

ATP-sensitive K+ channels, termed KATP channels, provide a link between cellular metabolism and membrane electrical activity in a variety of tissues. Channel isoforms have been identified and are targets for compounds that both stimulate and inhibit their activity resulting in membrane hyperpolarization and depolarization, respectively. Examples include relaxation of vascular smooth muscle and stimulation of insulin secr Read More

Searching the DNA database has led to the identification of a class of K+ channels now referred to as two-pore or tandem-pore domain K+ (K2P) channels. The K2P channel is structurally unique in that each subunit possesses two poreforming domains and four transmembrane segments. In mammals, sixteen K2P channel genes have been identified, and their mRNA transcripts are expressed in many different cell types and ti Read More

Idiopathic epilepsies are genetically determined diseases of the central nervous system characterized by typical epileptic seizures and EEG abnormalities but not associated with structural brain lesions. In recent years, an increasing number of mutations associated with idiopathic epilepsy syndromes were identified in genes encoding subunits of voltageor ligand-gated ion channels. These encouraging results provid Read More

The passage of ions to form and maintain electrochemical gradients is a key element for regulating cellular activities and is dependent on specific channel proteins or complexes. Certain ion channels have been the targets of pharmaceuticals that have had impact on a variety of cardiovascular and neurological diseases. Chloride channels regulate the movement of a major cellular anion, and in so doing they in part determine ce Read More

The molecular identification of novel ion channels expressed in the immune context provides very attractive potential targets for new therapeutic drugs designed to modulate immune system function. Several members of the recently discovered TRPM family of cation channels are expressed in immune cells. The TRPM channels show an astonishing diversity regarding their gating mechanisms and permeability profiles. First fun Read More

The MEK/MAPK signaling module is a key integration point along signal transduction cascades that regulate cell growth, survival, and differentiation, and is aberrantly activated in many human tumors. In tumor cells, constitutive MAPK activation affords increased proliferation and resistance to apoptotic stimuli, including classical cytotoxic drugs. In most instances, however, MAPK inhibition has cytostatic rather than cytotoxic eff Read More

It is well documented that sensory transmission, including pain, receives endogenous inhibitory modulatory influences at dorsal horn of the spinal cord. Recent results, from behavioral to molecular studies, demonstrate that injury caused plastic changes in forebrain areas. In addition to encoding pain, these supraspinal areas may also affect pain transmission in the spinal cord level by activating “top-down” descending fa Read More