Age-related quinidine effects on ionic currents of rabbit cardiac myocytes.
Age-related cardiac actions of quinidine have been shown in prolongation of action potential duration, but not in the tonic and use-dependent block of the maximal velocity of action potential upstroke. To elucidate the underlying ionic mechanisms, currents through the Na, Ca and K channels were examined by using a whole-cell voltage clamp technique on isolated neonatal (< 5 day) and adult (> 3 months) rabbit cardiac myocytes under various concentrations (0.5, 1.5 and 4.5 microM) of quinidine. In neonatal and adult myocytes, quinidine caused a comparable degree of dose-dependent effects on Na currents including decrease in peak Na currents, left-shift of steady-state availability curve and slowing of the recovery from inactivation. However, the inwardly rectifier K current and the transient outward current were suppressed to a greater extent in the neonatal myocytes than in the adult (P = 0.0002 and 0.02, respectively). On the contrary, the magnitude of decrease in peak Ca currents after quinidine treatment was much smaller in the neonatal myocytes than in the adult (P = 0.01). These findings indicate that age-related ionic channel-block by quinidine is complex; and shows major differences in the Ca and K currents of cardiac myocytes. Accordingly, a differential therapeutic potential of quinidine may exist in hearts of different ages.
Wu
M H
MH
Department of Pediatrics, National Taiwan University, Taipei, Republic of China.
Su
M J
MJ
Lue
H C
HC
D000200:Action Potentials / Q000187:drug effects; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology*; D011817:Rabbits; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D011802:Quinidine