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.
Guo
J
J
Department of Physiology, Faculty of Medicine, Kyoto University, Japan.
Ono
K
K
Noma
A
A
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D003971:Diastole / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology; D009529:Nicardipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012849:Sinoatrial Node / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D015220:Calcium Channels; D013779:Tetrodotoxin; D012964:Sodium; D009529:Nicardipine; D008274:Magnesium; D007545:Isoproterenol; D011188:Potassium; D002118:Calcium