title: Sustained subthreshold-for-twitch depolarization in rat single ventricular myocytes causes sustained calcium channel activation and sarcoplasmic reticulum calcium release.
abstract: Single rat ventricular myocytes, voltage-clamped at -50 to -40 mV, were depolarized in small steps in order to define the mechanisms that govern the increase in cytosolic [Ca2+] (Cai) and contraction, measured as a reduction in myocyte length. Small (3-5 mV), sustained (seconds) depolarizations that caused a small inward or no detectable change in current were followed after a delay by small (less than 2% of the resting length), steady reductions in cell length measured via a photodiode array, and small, steady increases in Cai measured by changes in Indo-1 fluorescence. Larger (greater than -30 and less than -20 mV), sustained depolarizations produced phasic Ca2+ currents, Cai transients, and twitch contractions, followed by a steady current and a steady increase in Cai and contraction. Nitrendipine (or Cd, verapamil, or Ni) abolished the steady contraction and always produced an outward shift in steady current. The steady, nitrendipine-sensitive current and sustained increase in Cai and contraction exhibited a similar voltage dependence over the voltage range between -40 and -20 mV. 2 microM ryanodine in the presence of intact Ca2+ channel activity also abolished the steady increase in Cai and contraction over this voltage range. We conclude that when a sustained depolarization does not exceed about -20 mV, the resultant steady, graded contraction is due to SR Ca2+ release graded by a steady ("window") Ca2+ current. The existence of appreciable, sustained, graded Ca2+ release in response to Ca2+ current generated by arbitrarily small depolarizations is not compatible with any model of Ca2(+)-induced Ca2+ release in which the releasing effect of the Ca2+ channel current is mediated solely by Ca2+ entry into a common cytosolic pool. Our results therefore imply a distinction between the triggering and released Ca2+ pools.
authors.affiliation: Laboratory of Cardiovascular Science, National Institute of Aging, National Institutes of Health, Baltimore, Maryland 21224.
authors.forename: A
authors.initials: A
authors.lastname: Talo
authors.forename: M D
authors.initials: MD
authors.lastname: Stern
authors.forename: H A
authors.initials: HA
authors.lastname: Spurgeon
authors.forename: G
authors.initials: G
authors.lastname: Isenberg
authors.forename: E G
authors.initials: EG
authors.lastname: Lakatta
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D009568:Nitrendipine / Q000494:pharmacology; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D009568:Nitrendipine; D002118:Calcium