title: Abnormal pacemaking is modulated by sarcoplasmic reticulum in partially-depolarized myocardium from dilated right atria in humans.
abstract: Fifty human atrial specimens removed at time of cardiac surgery were studied in vitro. Thirty-four samples were selected as presenting partial cell depolarization and exhibiting slow response action potentials. Twenty of these preparations were automatic whereas 14 were not. Neither mean maximum diastolic potential (-52.8 +/- 1.3 mV and -49.3 +/- 2.2 mV respectively) nor maximum rate of depolarization (Vmax) (1.1 +/- 0.1 V/s and 1.3 +/- 0.8 V/s) significantly differed between these two groups. Abnormal automaticity due to phase 4 depolarization occurred in 12/13 preparations dissected from markedly dilated atria whereas it occurred in only 2/10 preparations sampled from non-dilated atria. A statistically significant relationship between in vitro abnormal pacemaking and atrial dilatations was found. We investigated the effects on abnormal pacemaker depolarization and automaticity of a reduction in the extracellular Na and Ca and of sarcoplasmic reticulum (SR) inhibitors. Abnormal pacemaker depolarization appeared to be much more sensitive to a reduction in the extracellular Na than in the extracellular Ca. Both Sr and Mg slowed the automatic rate. Ryanodine 3 X 10(-6) M, a specific SR inhibitor, irreversibly lengthened the spontaneous basic cycle duration to about 300% of control. Epinephrine up to 10(-4) M was ineffective in accelerating the residual spontaneous rhythm that persists after ryanodine action, although epinephrine markedly enhanced the overshoot and Vmax of the slow responses. It is concluded that, in the human atrial myocardium, abnormal pacemaking that develops at low level of membrane potential: is promoted by chamber dilatation; is strongly modulated by SR-dependent processes.
mesh_terms: D000293:Adolescent; D000328:Adult; D002118:Calcium / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004108:Dilatation, Pathologic; D004594:Electrophysiology; D006325:Heart Atria / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D006331:Heart Diseases / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*
chemical_list: D012433:Ryanodine; D002118:Calcium