Effects of sympathetic nerve stimulation on membrane potential, [Ca2+](i),and force in the toad sinus venosus

The effects of sympathetic nerve stimulation on beat rate, force, intracell ular Ca2+ concentration ([Ca2+](i)) measured using fura 2, and membrane pot ential were recorded from the spontaneously beating toad sinus venosus. Sho rt trains of stimuli evoked an increase in the beat rate and force. During this tachycardia the amplitude of pacemaker action potentials was not chang ed, but there was an increase in the basal level of [Ca2+](i) with little c hange in peak [Ca2+](i) measured during each action potential. Depletion of intracellular Ca2+ stores with caffeine (3 mM) abolished all responses to sympathetic nerve stimulation. The effects of caffeine were fully reversibl e. Caffeine (3 mM), in the presence of the Ca2+-ATPase inhibitor thapsigarg in (30 mu M), abolished irreversibly the chronotropic and inotropic respons es evoked by sympathetic nerve stimulation. Ryanodine (10 mu M) attenuated, but did not abolish, these responses. These results suggest that, in the t oad sinus venosus, increases in force and beat rate evoked by sympathetic n erve stimulation result from the release of Ca2+ from intracellular Ca2+ st ores.