Calcium currents and arrhythmias: insights from molecular biology.
Calcium channels are critical to normal cardiac function. They are involved in the generation and conduction of the action potential and in contraction. Three surface membrane channels have been identified. The L-type Ca channel is most abundant and is responsible for Ca entry into the cell that triggers contraction. T-type Ca channels are most prevalent in the conduction system and are probably involved in automaticity. A newly described TTX-sensitive calcium current may be important in "boosting" or enhancing conduction and contraction. The main intracellular Ca channel resides in the sarcoplasmic reticulum and is responsible for the release of the Ca that activates contraction. Oscillatory behavior of this channel influences the sarcolemmal membrane, causing delayed aftercontractions and arrhythmias such as those seen in digoxin toxicity. The on-going molecular characterization of these channels will enhance our knowledge of their normal function and dysfunction in disease states, leading to the development of new therapeutic agents to treat arrhythmias and contractile dysfunction.
Shorofsky
S R
SR
Departments of Physiology and Medicine, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Balke
C W
CW
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000378:metabolism*; D020013:Calcium Signaling; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013329:Structure-Activity Relationship; D009626:Terminology as Topic; D013779:Tetrodotoxin / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D019837:Ryanodine Receptor Calcium Release Channel; D013779:Tetrodotoxin; D015544:Inositol 1,4,5-Trisphosphate; D008274:Magnesium; D002118:Calcium