Abstract
Two types of the late Na channels, burst and background, were studied in Purkinje and ventricular cells. In the whole-cell configuration, steady-state Na currents were recorded at potentials (-70 to -80 mV) close to the normal cell resting potential. The question of the contribution of late Na channels to this background Na conductance was investigated. During depolarization, burst Na channels were active for periods (up to approximately 5 s), which exceeded the action potential duration. However, they eventually closed without reopening, indicating the presence of slow and complete inactivation. When, at the moment of burst channel opening, the potential was switched to -80 mV, the channel closed quickly without reopening. We conclude that the burst Na channels cannot contribute significantly to the background Na conductance. Background Na channels undergo incomplete inactivation. After a step depolarization, their activity decreased in time, approaching a steady-state level. Background Na channel openings could be recorded at constant potentials in the range from -120 to 0 mV. After step depolarizations to potentials near -70 mV and more negative, a significant fraction of Na current was carried by the background Na channels. Analysis of the background channel behavior revealed that their gating properties are qualitatively different from those of the early Na channels. We suggest that background Na channels represent a special type of Na channel that can play an important role in the initiation of cardiac action potential and in the TTX-sensitive background Na conductance.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Attwell D., Cohen I., Eisner D., Ohba M., Ojeda C. The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres. Pflugers Arch. 1979 Mar 16;379(2):137–142. doi: 10.1007/BF00586939. [DOI] [PubMed] [Google Scholar]
- Baumgarten C. M., Singer D. H., Fozzard H. A. Intra- and extracellular potassium activities, acetylcholine and resting potential in guinea pig atria. Circ Res. 1984 Jan;54(1):65–73. doi: 10.1161/01.res.54.1.65. [DOI] [PubMed] [Google Scholar]
- Brown A. M., Lee K. S., Powell T. Sodium current in single rat heart muscle cells. J Physiol. 1981 Sep;318:479–500. doi: 10.1113/jphysiol.1981.sp013879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Callewaert G., Carmeliet E., Vereecke J. Single cardiac Purkinje cells: general electrophysiology and voltage-clamp analysis of the pace-maker current. J Physiol. 1984 Apr;349:643–661. doi: 10.1113/jphysiol.1984.sp015179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carmeliet E. Slow inactivation of the sodium current in rabbit cardiac Purkinje fibres. Pflugers Arch. 1987 Jan;408(1):18–26. doi: 10.1007/BF00581835. [DOI] [PubMed] [Google Scholar]
- Coraboeuf E., Deroubaix E., Coulombe A. Effect of tetrodotoxin on action potentials of the conducting system in the dog heart. Am J Physiol. 1979 Apr;236(4):H561–H567. doi: 10.1152/ajpheart.1979.236.4.H561. [DOI] [PubMed] [Google Scholar]
- Deitmer J. W., Ellis D. The intracellular sodium activity of sheep heart Purkinje fibres: effects of local anaesthetics and tetrodotoxin. J Physiol. 1980 Mar;300:269–282. doi: 10.1113/jphysiol.1980.sp013161. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dudel J., Peper K., Rüdel R., Trautwein W. The effect of tetrodotoxin on the membrane current in cardiac muscle (Purkinje fibers). Pflugers Arch Gesamte Physiol Menschen Tiere. 1967;295(3):213–226. doi: 10.1007/BF01844101. [DOI] [PubMed] [Google Scholar]
- Gilliam F. R., 3rd, Starmer C. F., Grant A. O. Blockade of rabbit atrial sodium channels by lidocaine. Characterization of continuous and frequency-dependent blocking. Circ Res. 1989 Sep;65(3):723–739. doi: 10.1161/01.res.65.3.723. [DOI] [PubMed] [Google Scholar]
- Gilly W. F., Armstrong C. M. Threshold channels--a novel type of sodium channel in squid giant axon. 1984 May 31-Jun 6Nature. 309(5967):448–450. doi: 10.1038/309448a0. [DOI] [PubMed] [Google Scholar]
- Gintant G. A., Datyner N. B., Cohen I. S. Slow inactivation of a tetrodotoxin-sensitive current in canine cardiac Purkinje fibers. Biophys J. 1984 Mar;45(3):509–512. doi: 10.1016/S0006-3495(84)84187-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grant A. O., Starmer C. F. Mechanisms of closure of cardiac sodium channels in rabbit ventricular myocytes: single-channel analysis. Circ Res. 1987 Jun;60(6):897–913. doi: 10.1161/01.res.60.6.897. [DOI] [PubMed] [Google Scholar]
- Hurwitz J. L., Dietz M. A., Starmer C. F., Grant A. O. A source of bias in the analysis of single channel data: assessing the apparent interaction between channel proteins. Comput Biomed Res. 1991 Dec;24(6):584–602. doi: 10.1016/0010-4809(91)90042-u. [DOI] [PubMed] [Google Scholar]
- Imanishi S., Arita M. Factors related to the low resting membrane potentials of diseased human atrial muscles. Jpn J Physiol. 1987;37(3):393–410. doi: 10.2170/jjphysiol.37.393. [DOI] [PubMed] [Google Scholar]
- January C. T., Fozzard H. A. The effects of membrane potential, extracellular potassium, and tetrodotoxin on the intracellular sodium ion activity of sheep cardiac muscle. Circ Res. 1984 Jun;54(6):652–665. doi: 10.1161/01.res.54.6.652. [DOI] [PubMed] [Google Scholar]
- Kiyosue T., Arita M. Late sodium current and its contribution to action potential configuration in guinea pig ventricular myocytes. Circ Res. 1989 Feb;64(2):389–397. doi: 10.1161/01.res.64.2.389. [DOI] [PubMed] [Google Scholar]
- Kunze D. L., Lacerda A. E., Wilson D. L., Brown A. M. Cardiac Na currents and the inactivating, reopening, and waiting properties of single cardiac Na channels. J Gen Physiol. 1985 Nov;86(5):691–719. doi: 10.1085/jgp.86.5.691. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu Y. M., DeFelice L. J., Mazzanti M. Na channels that remain open throughout the cardiac action potential plateau. Biophys J. 1992 Sep;63(3):654–662. doi: 10.1016/S0006-3495(92)81635-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nilius B., Vereecke J., Carmeliet E. Different conductance states of the bursting Na channel in guinea-pig ventricular myocytes. Pflugers Arch. 1989 Jan;413(3):242–248. doi: 10.1007/BF00583536. [DOI] [PubMed] [Google Scholar]
- Patlak J. B., Ortiz M., Horn R. Opentime heterogeneity during bursting of sodium channels in frog skeletal muscle. Biophys J. 1986 Mar;49(3):773–777. doi: 10.1016/S0006-3495(86)83704-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patlak J. B., Ortiz M. Slow currents through single sodium channels of the adult rat heart. J Gen Physiol. 1985 Jul;86(1):89–104. doi: 10.1085/jgp.86.1.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Patlak J. B., Ortiz M. Two modes of gating during late Na+ channel currents in frog sartorius muscle. J Gen Physiol. 1986 Feb;87(2):305–326. doi: 10.1085/jgp.87.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Powell T., Terrar D. A., Twist V. W. Electrical properties of individual cells isolated from adult rat ventricular myocardium. J Physiol. 1980 May;302:131–153. doi: 10.1113/jphysiol.1980.sp013234. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saint D. A., Ju Y. K., Gage P. W. A persistent sodium current in rat ventricular myocytes. J Physiol. 1992;453:219–231. doi: 10.1113/jphysiol.1992.sp019225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shattock M. J., Matsuura H. Measurement of Na(+)-K+ pump current in isolated rabbit ventricular myocytes using the whole-cell voltage-clamp technique. Inhibition of the pump by oxidant stress. Circ Res. 1993 Jan;72(1):91–101. doi: 10.1161/01.res.72.1.91. [DOI] [PubMed] [Google Scholar]
- Sheu S. S., Korth M., Lathrop D. A., Fozzard H. A. Intra- and extracellular K+ and Na+ activities and resting membrane potential in sheep cardiac purkinje strands. Circ Res. 1980 Nov;47(5):692–700. doi: 10.1161/01.res.47.5.692. [DOI] [PubMed] [Google Scholar]