Abstract
Voltage clamp experiments were carried out on the sinus venosus of the frog by means of the double mannitol gap technique. The ionic mechanism underlying the slowly hyperpolarization-activated inward current was investigated by changing the concentration and species of alkali cations and divalent cations in the bathing solution. Adding Rb or Cs in concentration of 10–20 mM to the control solution led to a dose-dependent increase in the inward current, as does elevating the external concentration of K from 2.5 to 25 mM. After the inward current had been nearly supressed by completely substituting Tris for Na in the external medium, it was partially restored after a subsequent addition of K, Rb or Cs to the Na-free medium. Various alkaline earths or transition metals added to the bathing solution markedly depressed the magnitude of the inward current. This inhibitory effect varied with concentration and nature of divalent cations added. It also depended on the concentration and species of alkali cations present in the external solution. From these observations it was proposed that the conductance responsible for the inward rectification in frog sinus venosus does not discriminate among monovalent cations. The results support the existence of a weak-field-strength site located in the permeation pathway. Divalent cation may exert their inhibitory effect by competing with permeant ions for this site.
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References
Adams PR, Halliwell JV (1982) A hyperpolarization-induced inward current in hippocampal pyramidal cells. J Physiol (Lond) 324:62P-63P
Adams DJ, Dwyer TM, Hille B (1980) The permeability of endplate channels to monovalent and divalent metal cations. J Gen Physiol 75:493–510
Bader CR, Bertrand D (1984) Effects of changes in intra and extracellular sodium on the inward (anomalous) rectification in salamander photoreceptors. J Physiol (Lond) 347:611–631
Bamberg E, Laüger P (1977) Blocking of the gramicidin channel by divalent cations. J Membr Biol 35:351–375
Brown HF, DiFrancesco D (1980) Voltage-clamp investigations of membrane currents underlying pace-maker activity in rabbit sino-atrial node. J Physiol (Lond) 308:331–351
Brown HF, Giles W, Noble SJ (1977) Membrane currents underlying activity in frog sinus venosus. J Physiol (Lond) 271:783–816
Brown HF, DiFrancesco D, Tromba C (1986) Recording of singlei f channels in isolated rabbit sino-atrial node cells. J Physiol (Lond) 377:111P
Callewaert G, Carmeliet E, Vereecke J (1984) Single cardiac Purkinje cells: general electrophysiology and voltage clamp analysis of the pace-maker current. J Physiol (Lond) 349:643–661
Champigny G, Lenfant J (1986) Block and activation of the hyperpolarization-activated inward current by Ba and Cs in frog sinus venosus. Pflügers Arch 407:684–690
Crepel F, Penit-Soria J (1986) Inward rectification and low threshold calcium conductance in rat cerebellar Purkinje cells. An in vitro study. J Physiol (Lond) 372:1–23
DiFrancesco D (1981) A new interpretation of the pace-maker current in calf Purkinje fibres. J Physiol (Lond) 314:359–376
DiFrancesco D (1981) Characterization of single pace-maker channels in cardiac sino-atrial node cells. Nature 324:470–473
DiFrancesco D, Ojeda C (1980) Properties of the currenti f in the sino-atrial node of the rabbit compared with those of the currenti K2 in Purkinje fibers. J Physiol (Lond) 308:353–367
DiFrancesco D, Ferroni A, Mazzani M, Tromba C (1986) Properties of the hyperpolarizing-activated current (i f) in cells isolated from the rabbit sino-atrial node. J Physiol (Lond) 377:61–88
Diamond JM, Wright EM (1969) Biological membranes: The physical basis of ion and monoelectrolyte selectivity. Annu Rev Physiol 31:581–646
Eisenman G (1962) Cation selective glass electrodes and their mode of operation. Biophys J 2 (suppl 2):259–323
Hess P, Lansman JB, Tsien RW (1986) Calcium channel selectivity for divalent and monovalent cations. Voltage and concentration dependence of single channel in ventricular heart cells. J Gen Physiol 88:293–319
Hille B (1984) Ionic channels of excitable membranes. Sinauer Associates, Sunderland, MA, p 426
Kass RS, Tsien RW, Weingart R (1978) Ionic basis of transient inward current induced by strophantidin in cardiac Purkinje fibres. J Physiol 281:209–226
Kokubun S, Nishimura M, Noma A, Irisawa H (1982) Membrane currents in the rabbit atrioventricular node cells. Pflügers Arch 393:19–22
Lansman JB, Hess P, Tsien RW (1986) Blockade of current through single calcium channels by Cd2+, Mg2+ and Ca2+. Voltage and concentration dependence of calcium entry into the pore. J Gen Physiol 88:321–347
Matsuda H (1986) Sodium conductance in calcium channels of guinea-pig ventricular cells induced by removal of external calcium ions. Pflügers Arch 407:465–475
Mayer ML, Westbrook GL (1983) A voltage clamp analysis of inward (anomalous) rectification in mouse spinal sensory ganglion neurones. J Physiol (Lond) 340:19–45
Nakayama T, Kurachi Y, Noma A, Irisawa H (1984) Action potential and membrane currents of single pacemaker cells of the rabbit heart. Pflügers Arch 402:248–257
Nathan RD (1986) Two electrophysiologically distinct types of cultured pacemaker cells from rabbit sinoatrial node. Am J Physiol 250:H325-H329
Noma A, Irisawa H (1976) Membrane currents in the rabbit sinoatrial node cell as studied by the double microelectrode method. Pflügers Arch 364:45–52
Rougier O, Vassort G, Stampfli R (1968) Voltage clamp experiments on frog atrial heart muscle with the sucrose gap technique. Pflügers Arch 301:91–108
Seyama I (1976) Characteristics of the rectifying properties of the sino-atrial node cell of the rabbit. J Physiol (Lond) 255:379–397
Tanigushi J, Kokubun S, Noma A, Irisawa H (1981) Spontaneously active cells isolated from the sino-atrial and atrio ventricular nodes of the rabbit heart. Jpn J Physiol 31:547–558
Van Driessche W, Zeiske W (1985) Ca2+ sensitive, spontaneously fluctuating, cation channels in the apical membrane of the adult frog skin epithelium. Pflügers Arch 405:250–259
Yanagihara K, Irisawa H (1980) Inward current activated during hyperpolarization in the rabbit sino-atrial node cell. Pflügers Arch 385:11–19
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Champigny, G., Bois, P. & Lenfant, J. Characterization of the ionic mechanism responsible for the hyperpolarization-activated current in frog sinus venosus. Pflugers Arch. 410, 159–164 (1987). https://doi.org/10.1007/BF00581909
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DOI: https://doi.org/10.1007/BF00581909