Abstract
An analysis of the slowly inactivating Na current in rabbit cardiac Purkinje fibres was made, using the twomicroelectrode voltage clamp technique. The existence of the slowly inactivating Na current was demonstrated by recording TTX-sensitive currents. The current was sensitive to Na withdrawal and could be blocked by 0.1 mM Cd. The current-voltage relation extended over a broad range of potentials, as negative as −85 mV. The time course of inactivation consisted of different phases, with time constants differing as much as three orders of magnitude. Time constants of the first phase of slow inactivation increased at more positive potentials. Non-inactivating Na currents were observed in the threshold region. Recovery from inactivation was less complex. The voltage dependency of inactivation could be described by a sigmoidal curve with a half maximum potential of −75.6 mV and a slope factor of 6.3 mV. Deactivation was fast. The results suggest that at the microscopic level the Na channel shows multiple states of inactivation. At the macroscopic level the slowly inactivating Na current plays an important role in determining diastolic potential, pacemaker activity and plateau duration, and is fundamental in explaining the effect of local anesthetics and frequency of stimulation on action potential duration.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Adelman WJ, Palti Y (1969) The effects of external potassium and long duration voltage clamp conditioning on the amplitude of sodium currents in the giant axon of the squid, Loligo pealei. J Gen Physiol 54:589–606
Aldrich RW, Corey DP, Stevens CF (1983) A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature (Lond) 306:436–441
Attwell D, Cohen I, Eisner D, Ohba M, Ojeda C (1979) The steady state TTX-sensitive (“window”) sodium current in cardiac Purkinje fibres. Pflügers Arch 379:137–142
Benndorf K, Boldt W, Nilius B (1985) Sodium current in single myocardial mouse cells. Pflügers Arch 404:190–196
Benoit E, Corbier A, Dubois J-M (1985) Evidence for two transient sodium currents in the frog node of Ranvier. J Physiol (Lond) 361:339–360
Bodewei R, Hering S, Lemke B, Rosenshtraukh LV, Undrovinas AI, Wollenberger A (1982) Characterization of the fast sodium current in isolated rat myocardial cells: simulation of clamped membrane potential. J Physiol (Lond) 325:301–315
Brown AM, Lee KS, Powell T (1981) Sodium current in single rat heart muscle cells. J Physiol (Lond) 318:479–500
Cachelin QB, DePeyer JE, Kokubun S, Reuter H (1983) Sodium channels in cultured cardiac cells. J Physiol (Lond) 340:389–401
Carmeliet E (1984) Slow inactivation of the sodium current in rabbit cardiac Purkinje fibres. J Physiol (Lond) 353: 125P (Abstr)
Carmeliet E (1985) Slow decay of sodium current and effects of quinidine in rabbit cardiac Purkinje fibers. In: Zipes DP, Jalife J (eds) Cardiac electrophysiology and arrhythmias. Grune and Stratton, Orlando, pp 207–215
Carmeliet E, Saikawa T, (1982) Shortening of the action potential and reduction of pacemaker activity by lidocaine, quindine, and procainamide in sheep cardiac Purkinje fibers. An effect on Na or K current. Circ Res 50:257–272
Chandler WK, Meves H (1970) Slow changes in membrane permeability and long-lasting action potentials in axons perfused with flouride solutions. J Physiol (Lond) 211:707–728
Cohen I, Falk R, Kline R (1981) Membrane currents following activity in canine cardiac purkinje fibers. Biophys J 33:281–288
Colatsky TJ (1980) Voltage clamp measurements of sodium channel properties in rabbit cardiac Purkinje fibres. J Physiol (Lond) 305:215–234
Coraboeuf E, Deroubaix EG, Coulombe A (1979) Effect of tetrodotoxin on action potentials of the conducting system in dog heart. Am J Physiol 236:H561-H567
DiFrancesco D, Ferroni A, Visentin S, Zara A (1985) Cadmium-induced blockade of the cardiac fast Na channels in calf Purkinje fibres. Proc R Soc Lond B 223:475–484
Dudel J, Peper K, Rudel R, Trautwein W (1976) The effect of tetrodotoxin on the membrane current in cardiac muscle (Purkinje fibers). Pflügers Arch 295:213–226
Ebihara L, Johnson EA (1980) Fast sodium current in cardiac muscle. A quantitative description. Biophys J 32:779–790
Eisner DA, Lederer WJ, Vaughan-Jones RD (1981) The effects of rubidium ions and membrane potential on the intracellular sodium activity of sheep Purkinje fibres. J Physiol (Lond) 317:189–205
Fox JM (1976) Ultra-slow inactivation of the ionic currents through the membrane of myelinated nerve. Biochim Biophys Acta 426:232–244
Fozzard HA, Friedlander I, January CT, Makielski JC, Sheets MF (1984) Second-order kinetics of Na+ channel inactivation in internally dialysed canine cardiac Purkinje cells. J Physiol (Lond) 353:72P
Gintant GA, Datyner NB, Cohen IS (1984) Slow inactivation of tetrodotoxin-sensitive current in canine cardiac Purkinje fibers. Biophys J 45:509–512
Hess P, Lansman JB, Tsien RW (1984) Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature (Lond) 311:538–544
January CT, Fozzard HA (1984) The effects of membrane potential, extracellular potassium and tetrodotoxin on the intracellular sodium ion activity of sheep cardiac muscle. Circ Res 54:652–665
Kunze DL, Lacerda AE, Wilson DL, Brown AM (1985) Cardiac Na currents and the inactivating, re-opening, and waiting properties of single cardiac Na channels. J Gen Physiol 86:697–719
McAllister RE, Noble D, Tsien RW (1975) Reconstruction of the electrical activity of cardiac Purkinje fibres. J Physiol (Lond) 251:1–59
Nagy K, Kiss T, Hoff D (1983) Single Na channels in mouse neuroblastoma cell membrane: indications for two open states. Pflügers Arch 399:302–308
Narahashi T, Moore JW, Scott WR (1964) Tetrodotoxin blockage of sodium conductance increase in lobster giant axons. J Gen Physiol 47:965–974
Patlak JB, Ortiz M (1985) Slow currents through single sodium channels of the adult rat heart. J Gen Physiol 86:89–104
Reuter H (1968) Slow inactivation of currents in cardiac Purkinje fibres. J Physiol (Lond) 197:233–253
Saikawa T, Carmeliet E (1982) Slow recovery of the maximal rate of rise (V max) of the action potential in sheep cardiac Purkinje fibers. Pflügers Arch 394:90–93
Schauf CL, Pencek TL, Davis FA (1976) Slow sodium inactivation in Myxicola axons. Evidence for a second inactive state. Biophys J 16:771–778
Sheu S-S, Fozzard HA (1982) Transmembrane Na+ and Ca2+ electrochemical gradients in cardiac muscle and their relationship to force development. J Gen Physiol 80:325–351
Ten Eick R, Yeh J, Matsuki N (1984) Two types of voltage dependent Na channels suggested by differential sensitivity of single channels to tetrodotoxin. Biophys J 45:70–73
Zilberter TI, Timin EN, Bendukidze ZA, Burnashev NA (1982) Patch-voltage clamp method for measuring fast inward current in single rat heart muscle cells. Pflügers Arch 394:150–155
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Carmeliet, E. Slow inactivation of the sodium current in rabbit cardiac Purkinje fibres. Pflugers Arch. 408, 18–26 (1987). https://doi.org/10.1007/BF00581835
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00581835