title: On the mechanisms of post-rest adaptation in the isolated electrically driven left atria of rats.
abstract: We studied the role of the resting period (1, 2, 4, 8, 16 min; n = 6-7), external Ca2+ (0.2, 0.4, 0.6 g/l; n + 5-6), stimulation frequency (1, 2, 3 Hz; n = 6), 4-aminopyridine (4-AP, 2 mM; n = 5); theophylline (1 mM; n = 6), ouabain (5 microM; n = 6), and verapamil (1 microM; n = 6) on post-rest adaptation in the isolated left atria of rats driven electrically by a 2x threshold intensity for 2 ms. Resting periods resulted in three-phasic adaptive changes in contractility during the post-rest stimulation before normalization: P1, hypercontractile phase, an initial twitch potentiation; P2, post-rest hypocontractile decay reached after 8 to 12 single twitches; and P3, a late reactive hypercontractile phase marked less than that of P1 and gradually declining to the pre-resting level. P1 and P2 were augmented along with increasing the resting period from 1 min to 16 min, whereas t1 (time between P1 and P2) shortened and P2 and t2 (time between P2 and P3) were not affected. P1 and P3 to become more apparent after shifting the stimulation frequency from 1 Hz to 3 Hz, accompanied by a shortening of t1 and t2 (p < 0.05) and an insignificant reversal of P2. An increase in Ca2+ concentration by 2- or 3-fold at 2 Hz reduced P1 was and antagonized P2, while leaving other parameters almost unaffected. The reduction of P1 by Ca2+ became more prominent at 3 Hz. Exposure to 4-AP depressed P1 and P3 at 1 Hz, which was reversed by increasing the stimulation frequency--P3 tended to diminish, whereas t1 and t2 were shortened. Theophylline reduced P1 antagonized P2, and shortened t1 and t2 significantly, and a combination of theophylline and 4-AP augmented the effects. Ouabain increased P1 and P2 in a frequency-dependent manner; prolonged t2 at 1 Hz, but shortened t2 at higher frequencies. Verapamil inhibition of Ca2+ channels augmented P1 and t1 and reduced P2 and P3, and the effects on all three parameters were augmented by combined 4-AP/verapamil. We concluded that the post-rest adaptive changes in contractility are a consequence of phasic changes in sarcoplasmic Ca2+ concentration and that such changes reflect an imbalance between the release from and uptake into the sarcoplasmic reticulum of Ca2+ and transsarcolemmal Ca2+ loss.
authors.affiliation: Department of Pharmacology, Cerrahpasa Medical Faculty, University of Istanbul, Cerrahpasa-Istanbul, Turkey. tahic@istanbul.edu.tr
authors.forename: C
authors.initials: C
authors.lastname: Küçukhüseyin
authors.forename: H
authors.initials: H
authors.lastname: Oncel
authors.forename: C
authors.initials: C
authors.lastname: Silan
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012146:Rest / Q000502:physiology*; D013806:Theophylline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002316:Cardiotonic Agents; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D010042:Ouabain; D015761:4-Aminopyridine; D013806:Theophylline; D014700:Verapamil; D002118:Calcium