title: Inhibition of sarcoplasmic reticulum Ca(2+)-ATPase decreases atrioventricular node-paced heart rate in rabbits.
abstract: Recent data indicate that Ca(2+) cycling in isolated atrioventricular node (AVN) cells contributes to setting spontaneous rate. The aim of the present study was to extend this observation to the intact AVN in situ, by evaluating the effects of inhibiting sarcoplasmic reticulum Ca(2+) uptake with cyclopiazonic acid (CPA) on intact AVN spontaneous activity and its response to isoprenaline. A model of the AVN-paced heart was produced to investigate intact AVN automaticity, by surgical ablation of the sino-atrial node (SAN) in the rabbit Langendorff-perfused heart. Electrograms were recorded from a site close to the AVN (triangle of Koch), an atrial site above the AVN, the left atrium and right ventricle, enabling AVN pacing of the preparation to be confirmed. Before SAN ablation, the heart rate was 166.8 ± 5.4 beats min(-1). Ablation of the SAN was clearly indicated by a sudden and significant decrease of heart rate to 108.6 ± 9.6 beats min(-1) (P < 0.01, n = 10). Isoprenaline (100 nm) increased AVN rate to 187.8 ± 12.0 beats min(-1) after 1 min of application (P < 0.01, n = 10). Cyclopiazonic acid (10 and 30 μm) decreased AVN rate to 81.6 ± 4.8 (n = 9) and 77.4 ± 6.0 beats min(-1) (n = 7), respectively [P < 0.05, 10 or 30 μm CPA versus control (n = 10)] and also reduced the AVN rate increase in response to isoprenaline from 78.8 ± 10.0 to 46.8 ± 6.8 and 26.7 ± 5.3%, respectively (P < 0.01). These inhibitory effects of CPA on the intact AVN rate and its response to isoprenaline indicate that Ca(2+) cycling is important to the intact AVN spontaneous activity and its acceleration during sympathetic stimulation.
authors.affiliation: School of Physiology and Pharmacology, Medical Sciences Building, University of Bristol, Bristol BS8 1TD, UK.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Cheng
authors.forename: Godfrey L
authors.initials: GL
authors.lastname: Smith
authors.forename: Clive H
authors.initials: CH
authors.lastname: Orchard
authors.forename: Jules C
authors.initials: JC
authors.lastname: Hancox
authors.forename: Francis L
authors.initials: FL
authors.lastname: Burton
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012849:Sinoatrial Node / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D007211:Indoles; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D007545:Isoproterenol; D002118:Calcium; C000543:cyclopiazonic acid