The cytosolic Ca2+ serves an intracellular mediator for many extracellular signals. The receptors coupling via heterotrimeric G proteins to different …
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Cell Death Modulators for in vitro Apoptosis Models
Until the beginning of 1980s, nerve cell necrosis was thought to responsible for nerve cell death in human brain, stroke …
Continue readingRole of Voltage-Gated K+ Channels in the Pathophysiology of Spinal Cord Injury
Spinal cord injury (SCI) is a devastating condition afflicting over 13,000 people annually in North America and is an important cause of mortality and neurological morbidity1.
Although early pharmacological intervention after SCI with methylprednisolone2,3 or GM-1 ganglioside4 results in modest neurological improvement, the overall impact of these treatments remains minimal. Therefore, novel therapeutic approaches are required to improve the neurological outcome of these patients.
Continue readingMolecular Diversity of P2 Receptors
ATP is released into the extracellular milieu upon cell and tissue damage, secretory exocytosis or activation of plasma membrane transporters.
Many types of excitatory or non-excitatory cells maintain specific receptors to ATP or other nucleotides on their surface. Nucleotide receptors, also named P2, in contrast to P1 adenosine receptors, comprise two different families: ionotropic P2X receptors and metabotropic P2Y receptors.
Continue readingDendrotoxins: Powerful Blockers of Voltage-Gated K+ Channels
Dendrotoxins are a family of 7 kDa. homologous polypeptides isolated from both green and black mamba venoms (Dendroaspis sp.)1-3. They contain 57-61 amino acid residues in a single chain, crosslinked by three disulfide bridges. Several Dendrotoxins have been isolated and their amino acid sequences completely (see Table 1) , while β- and γ-Dendrotoxin have only been partially sequenced1-4.
Dendrotoxins were first discovered to facilitate the release of acetylcholine at the neuromuscular junction4,5. Later discoveries demonstrated their ability to selectively block some voltage-dependent K+ channels in nerve endings with high affinity2,5.
Continue readingGABAA receptors
GABA (γ-aminobutyric acid) is the essential inhibitory neurotransmitter in the vertebrate brain. It interacts with three kinds of receptors: Class …
Continue readingVoltage-Gated Cl– Channel Family
The voltage-gated Cl– channel (CLC) family in mammals contains at least nine different genes, encoding the Cl– channels CLC-Ka (CLC-K1), …
Continue readingRegional expression of cardiac ion channels and cardiac electrical activity
Important differences in electrophysiological properties have been noted between different regions of the heart. Electrophysiological heterogeneity has also been detected within different parts of a given tissue, such as the ventricular subendocardium, midmyocardium and subepicardium. Although many molecular candidates for native ionic currents have been identified, the molecular basis of most currents is not completely understood. Heterogeneity of channel protein composition might well underlie the differences observed among the properties of ionic currents or the shape of the action potential in different regions of the heart. Techniques such as immunocytochemistry, immunohistochemistry and Western blotting have played an important role in identifying tissue expression of channel proteins as well as their cellular localization. This
Continue readingModulation of Heart Function by Natural Neurotoxins
Cardiac muscle cells (myocytes) are electrically excitable cells, interconnected in groups that respond to stimuli as a unit, contracting together whenever a single cell is stimulated.
Unlike the cells of other muscles and nerves, these cells show a spontaneous, intrinsic rhythm generated by specialized “pacemaker” cells, located in the sinoatrial (SA), and atrioventricular (AV) nodes of the heart. The cardiac cells also have an unusually long action potential, which can be divided into five phases (0 to 4)1,2.
Continue readingHCN Family: The Pacemaking Channels
The ability of excitable cells to generate rhythmic, spontaneously firing action potentials is called pacemaking. In heart, pacemaking is accomplished by rhythmic discharge of the sinoatrial node (SA node). The firing rate is determined by a specific current slowly depolarizing a membrane to the threshold level, triggering the action potential. The ionic conductance underlying the cardiac pacemaking was identified over 20 years ago and termed If (f for funny)1, 2. At the same time, a similar current was described in neurons and in retina, termed, respectively, Ih (h for hyperpolarization-activated) and Iq (q for queer)2. The unique features of If/Ih/Iq current are: (1) its activation by hyperpolarization; (2) conductance of Na+ and K+ ions (K+/Na+ ~3-4); (3) blocking by low concentration (0.1-5 mM) of extracellular Cs+; (4) enhancement by cyclic AMP
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