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BZ remodeling processes may promote or inhibit Ca\n                    <jats:sup>2+<\/jats:sup>\n                    and\/or repolarization alternans and may differentially affect ventricular arrhythmogenesis. Here, we used a detailed computational model of the canine ventricular cardiomyocyte to study the determinants of alternans in the BZ and their regulation by \u03b2-adrenergic receptor (\u03b2-AR) stimulation. The BZ model developed Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient alternans at slower pacing cycle lengths than the control model, suggesting that the BZ may promote spatially heterogeneous alternans formation in an infarcted heart. \u03b2-AR stimulation abolished alternans. By evaluating all combinations of downstream \u03b2-AR stimulation targets, we identified both direct (via ryanodine receptor channels) and indirect [via sarcoplasmic reticulum (SR) Ca\n                    <jats:sup>2+<\/jats:sup>\n                    load] modulation of SR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release as critical determinants of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient alternans. These findings were confirmed in a human ventricular cardiomyocyte model. Cell-to-cell coupling indirectly modulated the likelihood of alternans by affecting the action potential upstroke, reducing the trigger for SR Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release in one-dimensional strand simulations. However, \u03b2-AR stimulation inhibited alternans in both single and multicellular simulations. Taken together, these data highlight a potential antiarrhythmic role of sympathetic hyperinnervation in the BZ by reducing the likelihood of alternans and provide new insights into the underlying mechanisms controlling Ca\n                    <jats:sup>2+<\/jats:sup>\n                    transient and repolarization alternans.\n                  <\/jats:p>\n                  <jats:p>NEW &amp; NOTEWORTHY We integrated, for the first time, postmyocardial infarction electrical and autonomic remodeling in a detailed, validated computer model of \u03b2-adrenergic stimulation in ventricular cardiomyocytes. Here, we show that \u03b2-adrenergic stimulation inhibits alternans and provide novel insights into underlying mechanisms, adding to a recent controversy about pro-\/antiarrhythmic effects of postmyocardial infarction hyperinnervation.<\/jats:p>\n                  <jats:p>Listen to this article\u2019s corresponding podcast at http:\/\/ajpheart.podbean.com\/e\/%CE%B2-ar-stimulation-and-alternans-in-border-zone-cardiomyocytes\/ .<\/jats:p>","DOI":"10.1152\/ajpheart.00094.2017","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T20:40:34Z","timestamp":1495831234000},"page":"H338-H353","source":"Crossref","is-referenced-by-count":24,"title":["\u03b2-Adrenergic receptor stimulation inhibits proarrhythmic alternans in postinfarction border zone cardiomyocytes: a computational analysis"],"prefix":"10.1152","volume":"313","author":[{"given":"Jakub","family":"Tomek","sequence":"first","affiliation":[{"name":"Life Sciences Interface Doctoral Training Centre, University of Oxford, Oxford, United Kingdom;"},{"name":"Department of Physiology, Anatomy and Genetics, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blanca","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Computer Science, British Heart Foundation Centre of Research Excellence, University of Oxford, Oxford, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Bub","sequence":"additional","affiliation":[{"name":"Department of Physiology, McGill University, Montreal, Quebec, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Heijman","sequence":"additional","affiliation":[{"name":"Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The 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