title: Induced automaticity in isolated rat atrial cells by incorporation of a stretch-activated conductance.
abstract: Stretch of the atrium and sympathetic activity have been implicated as substrates for atrial fibrillation. We investigate how a model of stretch in combination with sympathetic stimulation can induce automaticity in atrial cells. We adapted our coupling clamp circuit so that a model ionic current that represents stretch-activated channels (SACs) was injected into an isolated rat atrial cell in real time. This current was calculated as ISAC= GSAC (Vm-ESAC), where GSAC and ESAC are the conductance and reversal potential of SACs and Vm is the cell's membrane potential. Repetitive automaticity was induced by a sufficiently large GSAC and this critical value of GSAC was decreased by exposure to isoproterenol. The critical value of GSAC decreased from 0.63+/-0.05 nS (mean+/-SE) in control to 0.40+/-0.07 nS in isoproterenol (P<0.05). Additionally, after exposure to isoproterenol, automaticity continued after GSAC was no longer applied and was accompanied by delayed after-depolarizations. In three cells, repetitive automaticity could not be induced at any value of GSAC. Exposure to 10 nM isoproterenol converted these cells to cells with repetitive automaticity in response to GSAC. We conclude that automaticity can be induced in isolated rat atrial cells by application of a model of SACs. Exposure to isoproterenol enhances this effect.
authors.affiliation: Todd Franklin Cardiac Research Laboratory, The Sibley Heart Center, Department of Pediatrics, Emory University, 2040 Ridgewood Drive, Atlanta, GA 30322, USA.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Wagner
authors.forename: Rajiv
authors.initials: R
authors.lastname: Kumar
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Joyner
authors.forename: Yanggan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D006325:Heart Atria / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007545:Isoproterenol