Local Anesthetics Affect Gramicidin A Channels Via Membrane Electrostatic Potentials

Overview

Journal J Membr Biol

Date 2016 Sep 5

PMID 27592116

Citations 8

Authors

Svetlana S Efimova

Anastasiia A Zakharova

Ludmila V Schagina

Olga S Ostroumova

Affiliations

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Abstract

The effects of local anesthetics (LAs), including aminoamides and aminoesters, on the characteristics of single gramicidin A (GA) channels in 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayers were studied. Aminoamides, namely lidocaine (LDC), prilocaine (PLC), mepivacaine (MPV), and bupivacaine (BPV), reduced the conductance of GA channels. Aminoesters influenced the current fluctuations induced by GA differently; procaine (PC) did not affect the fluctuations, whereas tetracaine (TTC) distinctly reduced the conductance of single GA channels. Using electrophysiological technique, we estimated the changes in the membrane boundary potential at the adsorption of LAs; LDC, PLC, MPV, BPV, and TTC substantially increased, while PC did not affect it. To elucidate which component of the membrane boundary potential, the surface or dipole potential, is responsible for the observed effects of LAs, we employed a fluorescence assay. We found that TTC led to a significant increase in the membrane dipole potential, whereas the adsorption of LDC, PLC, MPV, BPV, and PC did not produce any changes in the membrane dipole potential. We concluded that aminoamides affected the surface potential of lipid bilayers. Together, these data suggest that the effects of LAs on the conductance of single GA channels are caused by their influence on membrane electrostatic potentials; the regulation of GA pores by aminoamides is associated with the surface potential of membranes, whereas TTC modulation of channel properties is predominantly due to changes in dipole potential of lipid bilayers. These data might provide some significant implications for voltage-gated ion channels of cell membranes.

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References

Andersen O, Koeppe 2nd R . Molecular determinants of channel function. Physiol Rev. 1992; 72(4 Suppl):S89-158. DOI: 10.1152/physrev.1992.72.suppl_4.S89. View

Maas A, Rispens P, Siggaard-Andersen O, ZIJLSTRA W . On the reliability of the Henderson-Hasselbalch equation in routine clinical acid-base chemistry. Ann Clin Biochem. 1984; 21 ( Pt 1):26-39. DOI: 10.1177/000456328402100105. View

Gross E, Bedlack Jr R, Loew L . Dual-wavelength ratiometric fluorescence measurement of the membrane dipole potential. Biophys J. 1994; 67(1):208-16. PMC: 1225351. DOI: 10.1016/S0006-3495(94)80471-0. View

Andersen O, Finkelstein A, Katz I, Cass A . Effect of phloretin on the permeability of thin lipid membranes. J Gen Physiol. 1976; 67(6):749-71. PMC: 2214976. DOI: 10.1085/jgp.67.6.749. View

Cseh R, Benz R . The adsorption of phloretin to lipid monolayers and bilayers cannot be explained by langmuir adsorption isotherms alone. Biophys J. 1998; 74(3):1399-408. PMC: 1299486. DOI: 10.1016/S0006-3495(98)77852-X. View

Tsuchiya H, Mizogami M . Interaction of local anesthetics with biomembranes consisting of phospholipids and cholesterol: mechanistic and clinical implications for anesthetic and cardiotoxic effects. Anesthesiol Res Pract. 2013; 2013:297141. PMC: 3794646. DOI: 10.1155/2013/297141. View

Weiser T . Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant Nav1.2 channels. Neurosci Lett. 2005; 395(3):179-84. DOI: 10.1016/j.neulet.2005.10.058. View

Paiva J, Paradiso P, Serro A, Fernandes A, Saramago B . Interaction of local and general anaesthetics with liposomal membrane models: a QCM-D and DSC study. Colloids Surf B Biointerfaces. 2012; 95:65-74. DOI: 10.1016/j.colsurfb.2012.02.027. View

Mojumdar E, Lyubartsev A . Molecular dynamics simulations of local anesthetic articaine in a lipid bilayer. Biophys Chem. 2010; 153(1):27-35. DOI: 10.1016/j.bpc.2010.10.001. View

10.

Gawrisch K, Ruston D, Zimmerberg J, Parsegian V, Rand R, Fuller N . Membrane dipole potentials, hydration forces, and the ordering of water at membrane surfaces. Biophys J. 1992; 61(5):1213-23. PMC: 1260386. DOI: 10.1016/S0006-3495(92)81931-8. View

11.

Rokitskaya T, Antonenko Y, Kotova E . Effect of the dipole potential of a bilayer lipid membrane on gramicidin channel dissociation kinetics. Biophys J. 1997; 73(2):850-4. PMC: 1180981. DOI: 10.1016/S0006-3495(97)78117-7. View

12.

Montal M, Mueller P . Formation of bimolecular membranes from lipid monolayers and a study of their electrical properties. Proc Natl Acad Sci U S A. 1972; 69(12):3561-6. PMC: 389821. DOI: 10.1073/pnas.69.12.3561. View

13.

Rostovtseva T, Aguilella V, Vodyanoy I, Bezrukov S, Parsegian V . Membrane surface-charge titration probed by gramicidin A channel conductance. Biophys J. 1998; 75(4):1783-92. PMC: 1299850. DOI: 10.1016/S0006-3495(98)77620-9. View

14.

Busath D, Thulin C, Hendershot R, Phillips L, Maughan P, Cole C . Noncontact dipole effects on channel permeation. I. Experiments with (5F-indole)Trp13 gramicidin A channels. Biophys J. 1998; 75(6):2830-44. PMC: 1299956. DOI: 10.1016/S0006-3495(98)77726-4. View

15.

Butterworth 4th J, Strichartz G . Molecular mechanisms of local anesthesia: a review. Anesthesiology. 1990; 72(4):711-34. DOI: 10.1097/00000542-199004000-00022. View

16.

Ragsdale D, McPhee J, Scheuer T, Catterall W . Molecular determinants of state-dependent block of Na+ channels by local anesthetics. Science. 1994; 265(5179):1724-8. DOI: 10.1126/science.8085162. View

17.

Strichartz G, Sanchez V, Arthur G, Chafetz R, Martin D . Fundamental properties of local anesthetics. II. Measured octanol:buffer partition coefficients and pKa values of clinically used drugs. Anesth Analg. 1990; 71(2):158-70. DOI: 10.1213/00000539-199008000-00008. View

18.

Hille B . Local anesthetics: hydrophilic and hydrophobic pathways for the drug-receptor reaction. J Gen Physiol. 1977; 69(4):497-515. PMC: 2215053. DOI: 10.1085/jgp.69.4.497. View

19.

Nilius B, Benndorf K, Markwardt F . Effects of lidocaine on single cardiac sodium channels. J Mol Cell Cardiol. 1987; 19(9):865-74. DOI: 10.1016/s0022-2828(87)80615-6. View

20.

Clarke R . Effect of lipid structure on the dipole potential of phosphatidylcholine bilayers. Biochim Biophys Acta. 1997; 1327(2):269-78. DOI: 10.1016/s0005-2736(97)00075-8. View