The sustained inward current and inward rectifier K+ current in pacemaker cells dissociated from rat sinoatrial node

1. Myocytes were dissociated from the sinoatrial (XA) node of rat heart usi ng a new enzymatic dissociation technique. Only a small number of isolated XA node myocytes showed regular rhythmic contractions and spontaneous actio n potentials, and these were used in the present study. 2. The spontaneous action potential was resistant to TTX, and the action po tential parameters were similar to those of rabbit and guinea-pig pacemaker cells. Major time- and voltage-dependent currents were the delayed rectifi er K+ current I-Kr, the L-type Ca2+ current I-Ca,I-L and the sodium current I-Na. The hyperoplarization-activated cation current (I-f) was recorded fr om similar to 50 % of the cells with hyperpolarization beyond -90 mV. 3. The instantaneous current jump at the onset of a hyperpolarizing pulse s howed inward rectification and was largely blocked by Ba2+. This Ba2+-sensi tive current corresponded well to the inward rectifier K+ current (I-K1), a lthough it was much smaller in amplitude than in the ventricle. 4. A sustained inward current was activated on depolarization from -80 mV t o the voltage range of slow diastolic depolarization. The current was block ed by nicardipine, enlarged by isoprenaline and was insensitive to removal of external Ca2+. These characteristics were similar to the sustained inwar d current, I-st, previously described in the rabbit and guinea pig SA node cells. 5. The role of I-st was considered by constructing empirical equations, whi ch were applied to the experimental record of the action potential. It is d emonstrated that the voltage-dependent activation of I-st constitutes a pos itive feedback loop with the depolarization of the membrane.