title: Two differential mechanisms of automaticity in diseased human atrial fibers.
abstract: The ionic mechanisms of automaticity in spontaneously active preparations (n = 38) from "diseased" human atria were investigated. The cycle length (CL) of the automatic action potential (AAP) ranged from 0.6 to 4.5 s (mean +/- S.D.: 2.0 +/- 1.0 s). The AAP from preparations obtained from non-digitalized patients (group 1, n = 29) showed various CLs, in that 16 patients had a CL longer than 2.0 s (slow-type AAP) while in tissues from the other 13 patients, the CL was 2.0 s or less (fast-type AAP). On the other hand, all preparations obtained from the digitalized patients prior to cardiac surgery (group 2, n = 9) had the fast-type AAP (CL less than or equal to 2.0 s). The slow-type AAP was accelerated and changed to the fast one after application of ouabain (1 microM) or by perfusing with 50% [Na+]o Tyrode solution. Ryanodine (1 microM), a specific inhibitor of calcium release from the sarcoplasmic reticulum (SR), markedly lengthened the CL of fast-type AAP, without affecting the slow-type AAP. In contrast, caffeine (15 mM) shortened the CL of the slow-type AAP and remarkably lengthened the CL of the fast-type AAP, as is the case in ryanodine. The rate of slow-type AAP was enhanced with an increase in [Ca2+]o and depressed with a decrease in [Ca2+]o or with application of diltiazem, a Ca2+ channel blocker. The slow-type AAP was changed to the fast-type AAP by stretching the preparation by about 20%. In vitro preparations excised from patients with dilated atria revealed a shorter CL of AAPs. We conclude that in "diseased" human atrial preparations, the ionic mechanism responsible for generation of slow- and fast-type automaticity differs. Slow automaticity (CL greater than 2.0 s) perhaps relates to activation of the slow inward Ca2+ current, while the fast-type automaticity (CL less than or equal to 2.0 s) is linked to cyclic increases in [Ca2+]i.
authors.affiliation: Department of Physiology, Faculty of Medicine, Medical College of Oita, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: S
authors.initials: S
authors.lastname: Imanishi
authors.forename: M
authors.initials: M
authors.lastname: Arita
authors.forename: T
authors.initials: T
authors.lastname: Hadama
authors.forename: J
authors.initials: J
authors.lastname: Shirabe
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000375:Aging / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002301:Cardiac Glycosides / Q000494:pharmacology; D004558:Electric Stimulation; D006321:Heart / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D008875:Middle Aged; D009206:Myocardium / Q000166:cytology*; D013565:Sympatholytics / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D002301:Cardiac Glycosides; D013565:Sympatholytics; D002118:Calcium