Swelling-activated chloride channels in cardiac physiology and pathophysiology.
Characteristics and functions of the cardiac swelling-activated Cl current (I(Cl,swell)) are considered in physiologic and pathophysiologic settings. I(Cl,swell) is broadly distributed throughout the heart and is stimulated not only by osmotic and hydrostatic increases in cell volume, but also by agents that alter membrane tension and direct mechanical stretch. The current is outwardly rectifying, reverses between the plateau and resting potentials (E(m)), and is time-independent over the physiologic voltage range. Consequently, I(Cl,swell) shortens action potential duration, depolarizes E(m), and acts to decrease cell volume. Because it is activated by stimuli that also activate cation stretch-activated channels, I(Cl,swell) should be considered as a potential effector of mechanoelectrical feedback. I(Cl,swell) is activated in ischemic and non-ischemic dilated cardiomyopathies and perhaps during ischemia and reperfusion. I(Cl,swell) plays a role in arrhythmogenesis, myocardial injury, preconditioning, and apoptosis of myocytes. As a result, I(Cl,swell) potentially is a novel therapeutic target.
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0551, USA. clive.baumgarten.vcu.edu
Clive M
CM
Baumgarten
Henry F
HF
Clemo
D000200:Action Potentials; D000818:Animals; D000838:Anions; D017209:Apoptosis; D001145:Arrhythmias, Cardiac / Q000473:pathology; D055592:Biophysical Phenomena; D001703:Biophysics; D002462:Cell Membrane / Q000378:metabolism; D018118:Chloride Channels / Q000737:chemistry*; D002712:Chlorides / Q000737:chemistry*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004594:Electrophysiology; D006321:Heart / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D020935:MAP Kinase Signaling System; D032342:Muscle Cells / Q000378:metabolism; D017202:Myocardial Ischemia; D009206:Myocardium / Q000473:pathology*; D010641:Phenotype; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011817:Rabbits; D013314:Stress, Mechanical; D013997:Time Factors
D000838:Anions; D018118:Chloride Channels; D002712:Chlorides; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C