title: Rate-dependency of action potential duration and refractoriness in isolated myocytes from the rabbit AV node and atrium.
abstract: During atrial fibrillation, ventricular rate is determined by atrioventricular nodal (AVN) conduction, which in part is dependent upon the refractoriness of single AVN cells. The aims of this study were to investigate the rate-dependency of the action potential duration (APD) and effective refractory period (ERP) in single myocytes isolated from the AV node and atrium of rabbit hearts, using whole cell patch clamping, and to determine the contribution of the 4-aminopyridine (4-AP)-sensitive current, I(TO1)to these relationships in the two cell types. AVN cells had a more positive maximum diastolic potential (-60+/-1 v-71+/-2 mV), lower V(max)(8+/-2 v 144+/-17 V/s) and higher input resistance [420+/-46 v 65+/-7 MOmega (mean+/-s.eP<0.05 n=9-33)], respectively, than atrial myocytes. Stepwise increases in rate from 75 beats/min caused activation failure and Wenckebach periodicity in AVN cells (at around 400 beats/min), but 1:1 activation in atrial cells (at up to 600 beats/min). Rate reduction from 300 to 75 beats/min shortened the ERP in both cell types (from 155+/-7 to 135+/-11 ms in AVN cells [P<0.05, n=6] and from 130+/-8 to 106+/-7 ms in atrial cells [P<0.05, n=10]). Rate increase from 300 to 480 and 600 beats/min shortened ERP in atrial cells, by 12+/-4% (n=8) and 26+/-7% (n=7), respectively (P<0.05). By contrast, AVN ERP did not shorten at rates >300 beats/min. In atrial cells, rate reduction to 75 beats/min caused marked shortening of APD(50)(from 51+/-6 to 29+/-6 ms, P<0. 05). 4-AP (1 m m) significantly prolonged atrial APD(50)at 75 beats/min (P<0.05, n=7), but not at 300 or 400 beats/min. In AVN cells, in contrast, there was less effect of rate change on APD, and 4-AP did not alter APD(50)at any rate. 4-AP also did not affect APD(90)or ERP in either cell type. In conclusion, a lack of ERP-shortening at high rates in rabbit single AVN cells may contribute to ventricular rate control. I(TO1)contributed to the APD(50)rate relation in atrial, but not AVN cells and did not contribute to the ERP rate relation in either cell type.
authors.affiliation: Department of Medical Cardiology, Royal Infirmary, 10 Alexandra Parade, Glasgow, G31 2ER, UK. A.J.Workman@clinmed.gla.ac.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Workman
authors.forename: K A
authors.initials: KA
authors.lastname: Kane
authors.forename: A C
authors.initials: AC
authors.lastname: Rankin
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016275:Atrial Function; D001283:Atrioventricular Node / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D004558:Electric Stimulation; D004594:Electrophysiology; D006325:Heart Atria / Q000187:drug effects; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits
chemical_list: D015761:4-Aminopyridine