Neuronal control of heart rate in isolated mouse atria

A novel mouse isolated atrial preparation with intact postganglionic autonomic innervation was used to investigate the neuronal control of heart rate. To establish whether autonomic activation was likely to alter heart rate by modulating the hyperpolarization-activated current (If), the L-type Ca2+ current (ICa,L), or the ACh-activated K+ current (IK,ACh), the effects of nerve stimulation (right stellate ganglion or right vagus, 1-30 Hz) and autonomic agonists (0.1 microM norepinephrine or 0.3 microM carbachol) on heart rate were investigated in the presence of inhibitors of these currents, cesium chloride (Cs+, 1 mM), nifedipine (200 nM), and barium chloride (Ba2+, 0.1 mM), respectively. The positive chronotropic response to stellate ganglion stimulation was reduced by approximately 20% with Cs+ and nifedipine (P < 0.05), whereas the heart rate response to norepinephrine was only reduced with Cs+ (P < 0.05). Ba2+ attenuated the decrease in heart rate with vagal stimulation and carbachol by approximately 60% (P < 0.05). These results are consistent with the idea that sympathetic nerve stimulation modulates If to increase heart rate in the mouse. Activation of ICa,L also appears to contribute to the sympathetic heart rate response. However, the decrease in heart rate with vagal stimulation or carbachol is likely to result primarily from the activation of IK,ACh.