Characterization of sodium inward currents and their responses to lidocaine in immature and mature rabbit ventricular myocytes.
Using the whole-cell voltage clamp method, sodium (Na) channel properties and their responses to lidocaine were studied in ventricular myocytes isolated from neonatal (N, < 3 days), infant (I, 10-17 days) and mature (M, > 3 months) rabbits. Developmental changes in the Na channels were characterized by a progressive right-shift in the inactivation curves and a faster recovery from inactivation. Lidocaine (10 microM) effectively reduced the peak Na currents in M myocytes, but had little affect on the current-voltage curve in N myocytes. The steady-state h inactivation curve shifted toward the left (ie, more negative potentials) after lidocaine, and the extent of the left-shift increased with maturation. Similarly, the magnitude of prolongation in Na channel recovery from inactivation by lidocaine increased with age. However, lidocaine at a higher concentration (30 microM) in N myocytes effectively blocked the Na channels, and the degree of suppression was comparable to that in M myocytes with 10 microM lidocaine. These data suggest that the Na channels of N myocytes per se are less sensitive to lidocaine. The results of this study indicate that the extent of Na channel inactivation becomes smaller during postnatal maturation. However, the Na channel of immature myocytes is less sensitive to the widely used Na channel blocker, lidocaine, which preferentially binds to the inactive state of the Na channel.
Wu
M H
MH
Department of Pediatrics, National Taiwan University Hospital, College of Medicine, Taipei, R.O.C.
Su
M J
MJ
Lue
H C
HC
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D006352:Heart Ventricles / Q000166:cytology*; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism
D015222:Sodium Channels; D008012:Lidocaine