Induced triggered activity in isolated rat cardiac cells by incorporation of a stretch activated conductance

Stretch of the myocardium, sympathetic activity and oxidative stress have been implicated as substrates for cardiac arrhythmias. We adapted our coupling clamp circuit so that a model ionic current that represents stretch-activated channels (SACs) was injected into an isolated rat cardiac cell in real time. This current was calculated as I_SAC=G_SAC*(V_m-E_SAC), where G_SAC and E_SAC are the stretch-activated conductance and reversal potential and V_m is the membrane potential. In atrial cells, repetitive automaticity was induced by G_SAC of sufficient magnitude. Isoproterenol decreased the value of G_SAC required for automaticity (from 0.55±0.06 nS to 0.33±0.004 nS, p<0.01). Additionally, delayed afterdepolarizations were seen in isoproterenol. In ventricular cells, G_SAC did not produce sustained automaticity, although some transient activity occurred at high levels of G_SAC (6.0±0.4 nS). In 100 μM H₂O₂ solution, the action potential prolonged but did not have early afterdepolarizations (EADs) without G_SAC. The combination of G_SAC and H₂O₂ consistently produced EADS at lower levels of G_SAC (3.2±0.5 nS, n=7, p<0.05). In conclusion, triggered activity can be induced in isolated rat cardiac cells by application of a model of SACs and exposure to sympathetic stimulation or oxidative stress enhances the effects of stretch.