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Pharmacological modification of sodium channels from the human heart atrium in planar lipid bilayers: electrophysiological characterization of responses to batrachotoxin and pentobarbital

Published online by Cambridge University Press:  30 June 2005

H. C. Wartenberg ,
J. P. Wartenberg  and
B. W. Urban
H. C. Wartenberg
Affiliation:
Rheinische Friedrich-Wilhelms-Universität Bonn, Klinik und Poliklinik für Anästhesiologie und spezielle Intensivmedizin, Bonn, Germany
J. P. Wartenberg
Affiliation:
Rheinische Friedrich-Wilhelms-Universität Bonn, Klinik und Poliklinik für Anästhesiologie und spezielle Intensivmedizin, Bonn, Germany
B. W. Urban
Affiliation:
Rheinische Friedrich-Wilhelms-Universität Bonn, Klinik und Poliklinik für Anästhesiologie und spezielle Intensivmedizin, Bonn, Germany
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Summary

Background and objective: To investigate the effects of barbiturates on batrachotoxin-modified sodium channels from different regions of the human heart. Single sodium channels from human atria were studied and compared with existing data from the human ventricle and from the central nervous system.

Methods: Sodium channels from preparations of human atrial muscle were incorporated into planar lipid bilayers in the presence of batrachotoxin, a sodium channel activator. The steady-state behaviour of single sodium channels was recorded in symmetrical 500 mmol NaCl before and after the addition of pentobarbital 0.34–1.34 mmol.

Results: The batrachotoxin-treated human atrial sodium channel had an average single-channel conductance of 23.8 ± 1.6 pS in symmetrical 500 mmol NaCl and a channel fractional open time of 0.83 ± 0.06. The activation mid-point potential was −98.0 ± 2.3 mV. Extracellular tetrodotoxin (a specific sodium channel blocking agent) blocked these channels with a k1/2 = 0.53 μmol at 0 mV. Pentobarbital reduced the time average conductance of single atrial sodium channels in a concentration-dependent manner (ID50 = 0.71 mmol). In the same way, the steady-state activation was shifted to more hyperpolarized potentials (−10.6 mV at 0.67 mmol pentobarbital).

Conclusions: The properties of batrachotoxin-modified sodium channels from human atrial tissue did not differ greatly from those described for ventricular sodium channels in the literature. Our data yielded no explanation for the observed functional diversity. However, cardiac sodium channels differ from those found in the central nervous system.

Keywords

ATRIAL FUNCTIONBIOLOGICAL TRANSPORT, ACTIVE, membrane potentialsMEMBRANE TRANSPORT PROTEINS, ion channels, sodium channelsVENTRICULAR FUNCTION
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 20 , Issue 5 , May 2003 , pp. 354 - 362
Copyright
2003 European Society of Anaesthesiology

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References

Vilin YY, Fujimoto E, Ruben PC. A novel mechanism associated with idiopathic ventricular fibrillation (IVF) mutations R1232W and T1620M in human cardiac sodium channels. Pflugers Arch 2001; 442: 204–211.Google Scholar
Kambouris NG, Nuss HB, Johns DC, Tomaselli GF, Marban E, Balser JR. Phenotypic characterization of a novel long-QT syndrome mutation (R1623Q) in the cardiac sodium channel. Circulation 1998; 97: 640–644.Google Scholar
Wang DW, Yazawa K, George AL, Bennett PB. Characterization of human cardiac Na+ channel mutations in the congenital long QT syndrome. Proc Natl Acad Sci USA 1996; 93: 13200–13205.Google Scholar
Liu DW, Gintant GA, Antzelevitch C. Ionic bases for electrophysiological distinctions among epicardial, midmyocardial, and endocardial myocytes from the free wall of the canine left ventricle. Circ Res 1993; 72: 671–687.Google Scholar
Catterall WA. Common modes of drug action on Na+ channels: local anesthetics, antiarrhythmics and anticonvulsants. Trends Pharmacol Sci 1987; 8: 57–65.Google Scholar
Krafte DS, Volberg WA, Rapp L, Kallen RG, Lalik PH, Ciccarelli RB. Stable expression and functional characterization of a human cardiac Na+ channel gene in mammalian cells. J Mol Cell Cardiol 1995; 27: 823–830.Google Scholar
Hille B. Ionic Channels of Excitable Membranes, 2nd edn. Sunderland, UK: Sinauer Associates, 1992.
Catterall WA. Structure and function of voltage-gated ion channels. Annu Rev Biochem 1995; 64: 493–531.Google Scholar
Gellens ME, George AL, Chen LQ, et al. Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. Proc Natl Acad Sci USA 1992; 89: 554–558.Google Scholar
Zamponi GW, Doyle DD, French RJ. Fast lidocaine block of cardiac and skeletal muscle sodium channels: one site with two routes of access. Biophys J 1993; 65: 80–90.Google Scholar
Wang DW, George AL, Bennett PB. Comparison of heterologously expressed human cardiac and skeletal muscle sodium channels. Biophys J 1996; 70: 238–245.Google Scholar
Nuss HB, Chiamvimonvat N, Perez-Garcia MT, Tomaselli GF, Marban E. Functional association of the beta 1 subunit with human cardiac (hH1) and rat skeletal muscle (mu 1) sodium channel alpha subunits expressed in Xenopus oocytes. J Gen Physiol 1995; 106: 1171–1191.Google Scholar
Fozzard HA, Hanck DA. Structure and function of voltage-dependent sodium channels: comparison of brain II and cardiac isoforms. Physiol Rev 1996; 76: 887–926.Google Scholar
Hiroe K, Hisatome I, Tanaka Y, et al. Tonic block of the Na+ current in single atrial and ventricular guinea-pig myocytes, by a new antiarrhythmic drug, Ro 22-9194. Fundam Clin Pharmacol 1997; 11: 402–407.Google Scholar
Wartenberg HC, Wartenberg JP, Urban BW. Human cardiac sodium channels are affected by pentobarbital. Eur J Anaesthesiol 2001; 18: 306–313.Google Scholar
Balser JR. Structure and function of cardiac sodium channels. Cardiavasc Res 1999; 42: 327–338.Google Scholar
Goldin AL. Diversity of mammalian voltage-gated sodium channels. Ann N Y Acad Sci 1999; 868: 38–50.Google Scholar
Lehmann-Horn F, Jurkat-Rott K. Voltage-gated ion channels and hereditary disease. Physiol Rev 1999; 79: 1317–1372.Google Scholar
Guo XT, Uehara A, Ravindran A, Bryant SH, Hall S, Moczydlowski E. Kinetic basis for insensitivity to tetrodotoxin and saxitoxin in sodium channels of canine heart and denervated rat skeletal muscle. Biochemistry 1987; 26: 7546–7556.Google Scholar
Mandel G. Tissue-specific expression of the voltage-sensitive sodium channel. J Membr Biol 1992; 125: 193–205.Google Scholar
Recio-Pinto E, Thornhill WB, Duch DS, Levinson SR, Urban BW. Neuraminidase treatment modifies the function of electroplax sodium channels in planar lipid bilayers. Neuron 1990; 5: 675–684.Google Scholar
Recio-Pinto E, Duch DS, Levinson SR, Urban BW. Purified and unpurified sodium channels from eel electroplax in planar lipid bilayers. J Gen Physiol 1987; 90: 375–395.Google Scholar
Duch DS, Recio-Pinto E, Frenkel C, Urban BW. Human brain sodium channels in bilayers. Brain Res 1988; 464: 171–177.Google Scholar
Wartenberg HC, Urban BW, Duch DS. Distinct molecular sites of anaesthetic action: pentobarbital block of human brain sodium channels is alleviated by removal of fast inactivation. Br J Anaesth 1999; 82: 76–80.Google Scholar
Frenkel C, Duch DS, Urban BW. Molecular actions of pentobarbital isomers on sodium channels from human brain cortex. Anesthesiology 1990; 72: 640–649.Google Scholar
Levinson SR, Duch DS, Urban BW, Recio-Pinto E. The sodium channel from Electrophorus electricus. Ann N Y Acad Sci 1986; 479: 162–178.Google Scholar
Renaud JF, Kazazoglou T, Lombet A, et al. The Na+ channel in mammalian cardiac cells. Two kinds of tetrodotoxin receptors in rat heart membranes. J Biol Chem 1983; 258: 8799–8805.Google Scholar
French RJ, Worley JF III, Krueger BK. Voltage-dependent block by saxitoxin of sodium channels incorporated into planar lipid bilayers. Biophys J 1984; 45: 301–310.Google Scholar
Green WN, Weiss LB, Andersen OS. Batrachotoxin-modified sodium channels in planar lipid bilayers. Characterization of saxitoxin- and tetrodotoxin-induced channel closures. J Gen Physiol 1987; 89: 873–903.Google Scholar
Moczydlowski E, Garber SS, Miller C. Batrachotoxin-activated Na+ channels in planar lipid bilayers. Competition of tetrodotoxin block by Na+. J Gen Physiol 1984; 84: 665–686.Google Scholar
Frenkel C, Wartenberg HC, Duch DS, Urban BW. Steady-state properties of sodium channels from healthy and tumorous human brain. Brain Res Mol Brain Res 1998; 59: 22–34.Google Scholar
Yang XC, Labarca C, Nargeot J, et al. Cell-specific post-translational events affect functional expression at the plasma membrane but not tetrodotoxin sensitivity of the rat brain IIA sodium channel alpha-subunit expressed in mammalian cells. J Neurosci 1992; 12: 268–277.Google Scholar
Arreola J, Spires S, Begenisich T. Na+ channels in cardiac and neuronal cells derived from a mouse embryonal carcinoma cell line. J Physiol (Lond) 1993; 472: 289–303.Google Scholar
Kiyosue T, Spindler AJ, Noble SJ, Noble D. Background inward current in ventricular and atrial cells of the guinea-pig. Proc R Soc Lond B Biol Sci 1993; 252: 65–74.Google Scholar
Schneider M, Proebstle T, Hombach V, Hannekum A, Rudel R. Characterization of the sodium currents in isolated human cardiocytes. Pflugers Arch 1994; 428: 84–90.Google Scholar
Cohen SA. Immunocytochemical localization of rH1 sodium channel in adult rat heart atria and ventricle. Presence in terminal intercalated disks. Circulation 1996; 94: 3083–3086.Google Scholar
Urban BW, Friederich P. Anesthetic mechanisms in-vitro and in general anesthesia. Toxicol Lett 1998; 100–101: 9–16.Google Scholar
Schulte am Esch J, Krause ET. Molecular effects and neuronal nets. Anasthesiol Intensivmed Notfallmed Schmerzther 2000; 35: 729–730.Google Scholar
Rehberg B, Urban BW, Duch DS. The membrane lipid cholesterol modulates anesthetic actions on a human brain ion channel. Anesthesiology 1995; 82: 749–758.Google Scholar
Wright SN, Wang SY, Xiao YF, Wang GK. State-dependent cocaine block of sodium channel isoforms, chimeras, and channels coexpressed with the beta1 subunit. Biophys J 1999; 76: 233–245.Google Scholar
Zamponi GW, Doyle DD, French RJ. State-dependent block underlies the tissue specificity of lidocaine action on batrachotoxin-activated cardiac sodium channels. Biophys J 1993; 65: 91–100.Google Scholar
French RJ, Doyle DD, Anscomb L, Lee MC, Mather KJ, Guo Y. Kinetic properties distinguish batrachotoxin-activated cardiac sodium channels from other subtypes in planar lipid bilayers. Biophys J 1990; 57: 297a.Google Scholar