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. ThisContinue reading
Issue No. 15
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.
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
The mechanism of water movement across cell membranes remained unclear until 1992, when the first water specific channel was identified …
In 1988, a 21-amino acid endothelium-derived bioactive peptide was cloned and named endothelin (ET)1. Later, two other isoforms differing from …
Acetylcholine, the major neurotransmitter in the central and the peripheral nervous system, can act through two kinds of receptors1: ionotropic …
Protein phosphorylation constitutes one of the most important molecular mechanisms by which extracellular signals produce their biological responses in eukaryotic cells. Stimulation of protein kinases is considered to be the most common activation mechanism in signal transduction systems1. The protein serine/threonine kinase can be classified by the nature of their second messenger activators:
An important family of membrane associated guanylate kinase proteins (MAGUK) are abundantly found in brain. They are also called SAP (synapse associated proteins) because of their location at synapses. The four identified members of this family (PSD95, CHAPSYN110, SAP102, SAP97) have three similar domains (PDZ) at N-terminus. At C-terminus, they have one SH3 domain as well as a guanylate kinase-like sequence. PDZ (PSD95-Dlg-Zo-1) domains are found in hundreds of proteins in various cells and tissues. The archetype of the MAGUK family, PSD95, which is found in brain synapses has been widely studied. Its X-ray structure shows a globular protein in which the C- and N-terminus are closed1,2. Studies reported interactions between a C-terminal tripeptide motif of T/SXV of NMDA receptor and PSD953,4,5 or other SAP