Abstract
The ionic selectivity of the hyperpolarizationactivated inward current (i f) channel to monovalent cations was investigated in single isolated sinoatrial node cells of the rabbit using the whole-cell patch-clamp technique. With a 140 mM K+ pipette, replacement of 90% external Na+ by Li+ caused a −24.5 mV shift of the fully activated current/voltage I/V curve without a significant decrease of the slope conductance. With a 140 mM Cs+ pipette, the i f current decreased almost proportionally to the decrease in external [Na+]o as Li+ was substituted. These responses are practically the same as those observed with N-methyl glucamine (NMG+) substitution, suggesting that the relative permeability of Li+ compared with Na+ for the i f channel is as low as that of NMG+. When Cs+ or Rb+ was substituted for internal K+, the fully activated I/V relationship for i f showed strong inward rectification with a positive reversal potential, indicating low permeability of the i f channel for Cs+ and Rb+. These results show that the i f channel is highly selective for Na+ and K+ and will not pass the similar ions Li+ and Rb+. Such a high degree of selectivity is unique and may imply that the structure of the i f channel differs greatly from that of other Na+ and K+ conducting channels.
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References
Adams DJ, Dwyer TM, Hille B (1980) The permeability of endplate channels to monovalent and divalent metal cations. J Gen Physiol 75:493–510
Carmeliet EE (1964) Influence of lithium ions on the transmembrane potential and cation content of cardiac cells. J Gen Physiol 47:501–530
Colquhoun D, Neher E, Reuter H, Stevens CS (1981) Inward current channels activated by intracellular Ca in cultured heart cells. Nature 294:752–754
Denyer JC, Brown HF (1990) Pacemaking in rabbit isolated sinoatrial node cells during Cs+ block of the hyperpolarization-activated current, i f. J Physiol (Lond) 429:401–409
DiFrancesco D (1981) A study of the ionic nature of the pacemaker current in calf Purkinje fibres. J Physiol (Lond) 314:377–393
DiFrancesco D (1982) Block and activation of the pacemaker channel in calf Purkinje fibres: effects of potassium, caesium and rubidium. J Physiol (Lond) 329:485–507
DiFrancesco D (1986) Characterization of single pacemaker channels in cardiac sinoatrial node cells. Nature 324:470–473
DiFrancesco D, Ferroni A, Mazzanti M, Tromba C (1986) Properties of the hyperpolarizing-activated current (i f) in cells isolated from the rabbit sinoatrial node. J Physiol (Lond) 377:61–88
Dwyer TM, Adams DJ, Hille B (1980) The permeability of endplate channels to organic cations in frog muscle. J Gen Physiol 75:469–492
Edman A, Grampp W (1989) Ion permeation through hyperpolarization-activated membrane channels (Q-channels) in the lobster stretch receptor neuron. Pflügers Arch 413:249–255
Frace AM, Maruoka F, Noma A (1992) External K+ increases Na+ conductance of the hyperpolarization-activated current in rabbit cardiac pacemaker cells. Pflügers Arch 421:94–96
Hagiwara H, Irisawa H, Kasanuki H, Hosoda S (1992) Background current in sinoatrial node cells of the rabbit heart. J Physiol (Lond) 448:53–72
Heckmann K (1972) Single-file diffusion. In: Kreuzer F, Slegers JFG (eds) Passive permeability of cell membranes (Biomembranes series vol 3). Plenum Press, New York, pp 127–153
Hille B (1992) Selective permeability: independence. In: Hille B (ed) Ionic channels of excitable membranes. Sinauer, Sunderland, pp 337–361
Hille B, Schwarz W (1978) Potassium channels as multi-ion single-file pores. J Gen Physiol 72:409–442
Ho WK, Brown HF, Noble D (1993) Internal K ions modulate the action of external cations on hyperpolarization-activated inward current in rabbit isolated sinoatrial node cells. Pflügers Arch 424:308–314
Keynes RD, Swan RC (1959) Permeability of frog muscle fibres to lithium ions. J Physiol (Lond) 147:626–638
Kimura H, Miyamae S, Noma A (1989) Identification of sodium-calcium exchange current in single ventricular cells of guinea-pig. J Physiol (Lond) 384:199–222
Langer GA (1982) Sodium-calcium exchange in the heart. Annu Rev Physiol 44:435–449
Läuger P (1973) Ion transport through pores: a rate-theory analysis. Biochim Biophys Acta 311:423–441
Läuger P (1980) Kinetic properties of ion carriers and channels. J Membr Biol 59:163–178
Ponce-Hornos JE, Langer GA (1980) Sodium-calcium exchange in mammalian myocardium: the effects of lithium. J Mol Cell Cardiol 12:1367–1382
Takeuchi A, Takeuchi N (1960) On the permeability of endplate membrane during the action of transmitter. J Physiol (Lond) 154:52–67
Tsien RW, Hess P, McCleskey EW, Rosenberg RL (1987) Calcium channels and mechanisms of selectivity, permeation, and block. Annu Rev Biophys Biophys Chem 16:265–290
Vassalle M (1970) Electrogenic suppression of automaticity in sheep and dog Purkinje fibres. Circ Res 27:361–377
Wollmuth LP, Hille B (1992) Ionic selectivity of I h channels of rod photoreceptors in tiger salamanders. J Gen Physiol 100:749–765
Yellen G (1982) Single Ca2+-activated nonselective cation channels in neuroblastoma. Nature 296:357–359
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Ho, W.K., Brown, H.F. & Noble, D. High selectivity of the i f channel to Na+ and K+ in rabbit isolated sinoatrial node cells. Pflugers Arch. 426, 68–74 (1994). https://doi.org/10.1007/BF00374672
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DOI: https://doi.org/10.1007/BF00374672