A sustained inward current activated at the diastolic potential range in rabbit sino‐atrial node cells.

1. After blocking both the hyperpolarization‐activated current and the membrane K+ conductance, depolarizations from ‐80 mV to between ‐70 and ‐50 mV induced a sustained current in sino‐atrial node cells. We have tentatively designated this current Ist. 2. Ist was blocked by both organic and inorganic Ca2+ channel blockers, but was insensitive to tetrodotoxin (30 microM). Isoprenaline increased Ist. 3. The peak of Ist (at about ‐50 mV) was increased to 149 +/‐ 13% (n = 8, P < 0.01) by lowering the external Ca2+ concentration ([Ca2+]o) from 1.8 to 0.1 mM, in contrast to the marked depression of the L‐type Ca2+ current. In 0.1 mM [Ca2+]o solution, the nicardipine‐sensitive current‐voltage relation showed the peak amplitude at about ‐50 mV and a reversal potential of +37.4 +/‐ 4.4 mV (n = 5). The isoprenaline‐sensitive component also showed a reversal potential of about +30 mV. 4. Reducing [Na+]o from 140 to 70 mM in 0.1 mM [Ca2+]o decreased Ist to 53 +/‐ 5% (n = 7, P < 0.01). Increasing [Ca2+]o or [Mg2+]o decreased the amplitude of Ist. The half‐maximum concentration of Mg2+ inhibition was 2.2 mM. 5. At 1.8 mM [Ca2+]o, Ist was inactivated by clamping for 5s at ‐10 mV, and gradually recovered after repolarization to ‐80 mV with a half‐time of 1.36 +/‐ 0.4 s (n = 6). 6. The transitional sino‐atrial node cell had minimal amplitude of Ist. 7. These characteristics of Ist are qualitatively comparable to those of the monovalent cation conductance of the L‐type Ca2+ channel induced by depleting external divalent cations to the micromolar range. We conclude that Ist is generated by a novel subtype of L‐type Ca2+ channel.