Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Spinelli, W. et al.

Reduction of Vmax by QX-314 and benzocaine in neonatal and adult canine cardiac Purkinje fibers.

The authors have previously shown that the use-dependent action of lidocaine on the Vmax of canine Purkinje fibers and on intraventricular conduction in the in situ heart undergoes significant developmental changes. In this study, they use standard microelectrode techniques to test whether these age-related differences are due to the charged, more hydrophilic form or to the uncharged, more lipophilic form of a local anesthetic. QX-314, a permanently charged lidocaine derivative, depressed Vmax to a significantly greater extent in adult than in neonatal Purkinje fibers. This difference was due to its use-dependent blocking action and not to its tonic blocking action. The kinetic time constant (tau on) for the development of use dependence was shorter in adults (90 +/- 9 vs. 134 +/- 15 beats; P less than .05), whereas the time constant for recovery from use dependence (tau off) was shorter in neonates (53 +/- 4 vs. 106 +/- 10 sec; P less than .05). QX-314 (3 X 10(-5) M) shifted the curve of Vmax vs. activation voltage in a hyperpolarizing direction by 16.2 +/- 2.4 mV in adults and 5.1 +/- 1.1 mV in neonates (P less than .05). In contrast, the uncharged tertiary amine benzocaine (1 X 10(-5)-5 X 10(-4) M) showed no developmental differences in its effects on Vmax. Adult and neonatal fibers showed comparable tonic block and no use-dependent block. These results extend those of the authors' previous studies and suggest that developmental differences in the action of local anesthetics depend primarily on the use-dependent action of the charged molecular form.[1]

References

Reduction of Vmax by QX-314 and benzocaine in neonatal and adult canine cardiac Purkinje fibers. Spinelli, W., Danilo, P., Rosen, M.R. J. Pharmacol. Exp. Ther. (1988) [Pubmed]

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