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Inhibition of cardiac Na + current by primaquine
Author(s) -
OrtaSalazar Gerardo,
Bouchard Ron A,
MoralesSalgado Fernando,
SalinasStefa Eduardo M
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704460
Subject(s) - primaquine , chemistry , flecainide , pharmacology , electrophysiology , myocyte , biophysics , cardiac muscle , contractility , cardiotoxicity , membrane potential , medicine , endocrinology , biochemistry , biology , toxicity , chloroquine , immunology , malaria , atrial fibrillation
The electrophysiological effects of the anti‐malarial drug primaquine on cardiac Na + channels were examined in isolated rat ventricular muscle and myocytes. In isolated ventricular muscle, primaquine produced a dose‐dependent and reversible depression of dV/dt during the upstroke of the action potential. In ventricular myocytes, primaquine blocked I Na + in a dose‐dependent manner, with a K d of 8.2 μ M . Primaquine (i) increased the time to peak current, (ii) depressed the slow time constant of I Na + inactivation, and (iii) slowed the fast component for recovery of I Na + from inactivation. Primaquine had no effect on: (i) the shape of the I – V curve, (ii) the reversal potential for Na + , (iii) the steady‐state inactivation and g Na + curves, (iv) the fast time constant of inactivation of I Na + , and (v) the slow component of recovery from inactivation. Block of I Na + by primaquine was use‐dependent. Data obtained using a post‐rest stimulation protocol suggested that there was no closed channel block of Na + channels by primaquine. These results suggest that primaquine blocks cardiac Na + channels by binding to open channels and unbinding either when channels move between inactivated states or from an inactivated state to a closed state. Cardiotoxicity observed in patients undergoing malaria therapy with aminoquinolines may therefore be due to block of Na + channels, with subsequent disturbances of impulse conductance and contractility.British Journal of Pharmacology (2002) 135 , 751–763; doi: 10.1038/sj.bjp.0704460