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Blockade of cardiac sodium channels by lidocaine. Single-channel analysis.

Publication ,  Journal Article
Grant, AO; Dietz, MA; Gilliam, FR; Starmer, CF
Published in: Circ Res
November 1989

The mechanism of interaction of lidocaine with cardiac sodium channels during use-dependent block is not well defined. We examined the blockade of single cardiac sodium channels by lidocaine and its hydrophobic derivative RAD-242 in rabbit ventricular myocytes. Experiments were performed in cell-attached and inside-out patches. Use-dependent block was assessed with trains of ten 200-msec pulses with interpulse intervals of 500 msec and test potentials of -60 to -40 mV. Single-channel kinetics sometimes showed time-dependent change in the absence of drug. During exposure to 80 microM lidocaine, use-dependent block during the trains was associated with a decrease in the average number of openings per step. At -60 mV, mean open time was not significantly changed (control, 1.4 +/- 0.6 msec; lidocaine, 1.2 +/- 0.3 msec, p greater than 0.05). Greater block developed during trains of 200-msec pulses compared with trains of 20-msec pulses at the same interpulse interval at test potentials during which openings were uncommon later than 20 msec (-50 and -40 mV). Prolonged bursts of channels showing slow-gating kinetics were observed both in control and the presence of 80 microM lidocaine. However, lidocaine may decrease the late sodium current by altering the kinetics of slow gating. The hydrophobic lidocaine derivative RAD-242, which has a 10-fold greater lipid solubility than lidocaine, decreased the peak averaged current during pulse train stimulation by 60% without a change in the mean open time. Our results suggest that the major effect of lidocaine during use-dependent block involves the interaction with a nonconducting state of the sodium channel followed by a failure to open during subsequent depolarization.

Duke Scholars

Published In

Circ Res

DOI

ISSN

0009-7330

Publication Date

November 1989

Volume

65

Issue

5

Start / End Page

1247 / 1262

Location

United States

Related Subject Headings

  • Time Factors
  • Sodium Channels
  • Myocardium
  • Lidocaine
  • Kinetics
  • Cardiovascular System & Hematology
  • Animals
  • 3202 Clinical sciences
  • 3201 Cardiovascular medicine and haematology
  • 1103 Clinical Sciences
 

Citation

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Grant, A. O., Dietz, M. A., Gilliam, F. R., & Starmer, C. F. (1989). Blockade of cardiac sodium channels by lidocaine. Single-channel analysis. Circ Res, 65(5), 1247–1262. https://doi.org/10.1161/01.res.65.5.1247
Grant, A. O., M. A. Dietz, F. R. Gilliam, and C. F. Starmer. “Blockade of cardiac sodium channels by lidocaine. Single-channel analysis.Circ Res 65, no. 5 (November 1989): 1247–62. https://doi.org/10.1161/01.res.65.5.1247.
Grant AO, Dietz MA, Gilliam FR, Starmer CF. Blockade of cardiac sodium channels by lidocaine. Single-channel analysis. Circ Res. 1989 Nov;65(5):1247–62.
Grant, A. O., et al. “Blockade of cardiac sodium channels by lidocaine. Single-channel analysis.Circ Res, vol. 65, no. 5, Nov. 1989, pp. 1247–62. Pubmed, doi:10.1161/01.res.65.5.1247.
Grant AO, Dietz MA, Gilliam FR, Starmer CF. Blockade of cardiac sodium channels by lidocaine. Single-channel analysis. Circ Res. 1989 Nov;65(5):1247–1262.

Published In

Circ Res

DOI

ISSN

0009-7330

Publication Date

November 1989

Volume

65

Issue

5

Start / End Page

1247 / 1262

Location

United States

Related Subject Headings

  • Time Factors
  • Sodium Channels
  • Myocardium
  • Lidocaine
  • Kinetics
  • Cardiovascular System & Hematology
  • Animals
  • 3202 Clinical sciences
  • 3201 Cardiovascular medicine and haematology
  • 1103 Clinical Sciences