Journal article
I-f and SR Ca2+ release both contribute to pacemaker activity in canine sinoatrial node cells
Journal of molecular and cellular cardiology, Vol.49(1), pp.33-40
07/01/2010
DOI: 10.1016/j.yjmcc.2010.03.019
PMCID: PMC2883640
PMID: 20380837
Abstract
Increasing evidence suggests that cardiac pacemaking is the result of two sinoatrial node (SAN) cell mechanisms a 'voltage clock' and a Ca2+ dependent process, or 'Ca2+ clock' The voltage clock initiates action potentials (APs) by SAN cell membrane potential depolarization from inward currents, of which the pacemaker current (I-f) is thought to be particularly important A Ca2+ dependent process triggers APs when sarcoplasmic reticulum (SR) Ca2+ release activates inward current carried by the forward mode of the electrogenic Na+/Ca2+ exchanger (NCX) However, these mechanisms have mostly been defined in rodents or rabbits, but are unexplored in single SAN cells from larger animals Here, we used patch-clamp and confocal microscope techniques to explore the roles of the voltage and Ca2+ clock mechanisms in canine SAN pacemaker cells We found that ZD7288, a selective I-f antagonist, significantly reduced basal automaticity and induced irregular, arrhythmia-like activity in canine SAN cells In addition, ZD7288 impaired but did not eliminate the SAN cell rate acceleration by isoproterenol In contrast, ryanodine significantly reduced the SAN cell acceleration by isoproterenol, while ryanodine reduction of basal automaticity was modest (similar to 14%) and did not reach statistical significance Importantly, pretreatment with ryanodine eliminated SR Ca2+ release, but did not affect basal or isoproterenol-enhanced I-f Taken together, these results indicate that voltage and Ca2+ dependent automaticity mechanisms coexist in canine SAN cells, and suggest that I-f and SR Ca2+ release cooperate to determine baseline and catecholamine-dependent automaticity in isolated dog SAN cells (C) 2010 Elsevier Ltd All rights reserved
Details
- Title: Subtitle
- I-f and SR Ca2+ release both contribute to pacemaker activity in canine sinoatrial node cells
- Creators
- Zhan Gao - University of IowaBiyi Chen - University of IowaMei-ling A. Joiner - University of IowaYuejin Wu - University of IowaXiaoqun Guan - University of IowaOlha M. Koval - University of IowaAshok K. Chaudhary - University of IowaShane R. Cunha - University of IowaPeter J. Mohler - University of IowaJames B. Martins - University of IowaLong-Sheng Song - University of IowaMark E. Anderson - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of molecular and cellular cardiology, Vol.49(1), pp.33-40
- Publisher
- Elsevier
- DOI
- 10.1016/j.yjmcc.2010.03.019
- PMID
- 20380837
- PMCID
- PMC2883640
- ISSN
- 0022-2828
- eISSN
- 1095-8584
- Number of pages
- 8
- Grant note
- Fondation Leducq Transatlantic Alliance University of Iowa Research Foundation R01 HL 079031; R01 HL 096652; R01 HL 070250 / National Institutes of Health (NIH); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HL079031 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 07/01/2010
- Academic Unit
- Cardiovascular Medicine; Biology; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984293082602771
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