期刊
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY
卷 98, 期 2-3, 页码 161-170出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbiomolbio.2009.01.010
关键词
Acetylcholine; Natriuretic peptides; Human atrium; Fibroblast; Mathematical model
资金
- NIH [R01-HL063195, R01-HL082729, R01-HL067322]
- NSF [CBET-0601935]
- Canadian Institutes of Health Research
- Stroke Foundation of Canada
- Alberta Heritage Foundation for Medical Research
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL063195, R01HL067322, R01HL082729] Funding Source: NIH RePORTER
In the mammalian heart, myocytes and fibroblasts can communicate via gap junction, or connexin-mediated current flow. Some of the effects of this electrotonic coupling on the action potential waveform of the human ventricular myocyte have been analyzed in detail. The present study employs a recently developed mathematical model of the human atrial myocyte to investigate the consequences of this heterogeneous cell-cell interaction on the action potential of the human atrium. TWO independent physiological processes which alter the physiology of the human atrium have been studied. i) The effects of the autonomic transmitter acetylcholine on the atrial action potential have been investigated by inclusion of a time-independent, acetylcholine-activated K+ current in this mathematical model of the atrial myocyte. ii) A non-selective cation current which is activated by natriuretic peptides has been incorporated into a previously published mathematical model of the cardiac fibroblast. These results identify subtle effects of acetylcholine, which arise from the nonlinear interactions between ionic currents in the human atrial myocyte. They also illustrate marked alterations in the action potential waveform arising from fibroblast-myocyte source-sink principles when the natriuretic peptide-mediated cation conductance is activated. Additional calculations also illustrate the effects Of Simultaneous activation of both of these cell-type specific conductances within the atrial myocardium. This study provides a basis for beginning to assess the utility of mathematical modeling in understanding detailed cell-cell interactions within the complex paracrine environment of the human atrial myocardium. (C) 2009 Published by Elsevier Ltd.
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