Další formáty:
BibTeX
LaTeX
RIS
@article{608107, author = {Nováková, Marie and Bébarová, Markéta and Pásek, Michal and Matejovič, Peter and Tarabová, Bohuslava and Lacinová, Lubica}, article_location = {Praha}, article_number = {3}, keywords = {sigma receptor; haloperidol; cardiac excitability}, language = {eng}, issn = {0862-8408}, journal = {Physiological Research}, title = {Effect of sigma receptor ligand haloperidol on cardiac excitability}, volume = {54}, year = {2005} }
TY - JOUR ID - 608107 AU - Nováková, Marie - Bébarová, Markéta - Pásek, Michal - Matejovič, Peter - Tarabová, Bohuslava - Lacinová, Lubica PY - 2005 TI - Effect of sigma receptor ligand haloperidol on cardiac excitability JF - Physiological Research VL - 54 IS - 3 SP - 36P EP - 36P PB - Inst of Physiology, Academy of Sciences SN - 08628408 KW - sigma receptor KW - haloperidol KW - cardiac excitability N2 - Sigma receptor ligand haloperidol is a psychotropic drug used in the treatment of various psychiatric disorders. Severe cardiovascular side effects (mostly ventricular arrhythmias) have been reported. Thus, we have investigated the effects of haloperidol on the sodium current INa and potassium currents, the transient outward current Ito, the current at the end of 250ms-impulse IK,end (that is mainly composed of the delayed rectifier current IK) and the inward rectifier current IK1. Experiments were performed on enzymatically isolated rat ventricular cardiomyocytes by whole cell patch clamp technique at room temperature. Haloperidol inhibited reversibly and in concentration-dependent manner amplitudes of all tested ion currents with 39% inhibition of INa, 39% inhibition of Ito and 14% inhibition of IK,end in the presence of 1 ľmol/l and 95% inhibition of INa, 80% inhibition of Ito, 37% inhibition of IK,end and 29 % inhibition of IK1 in the presence of 10 ľmol/l haloperidol. Inhibition of Ito was voltage-independent, with a small (-1.4 mV; P<0.05) hyperpolarizing shift of the steady state inactivation curve. The apparent inactivation of Ito was accelerated in the presence of haloperidol (t = 27.4 ą 3.3 ms in the absence and 6.9 ą 2.3 ms in the presence of 10 ľmol/l haloperidol). Inhibition of both other tested potassium currents IK,end and IK1 did not depend on membrane voltage as well. We conclude that haloperidol causes reversible and concentration-dependent inhibition of sodium and potassium membrane currents in rat ventricular cardiomyocytes with the highest effectivity on INa and Ito. In the case of potassium currents, the inhibition was voltage-independent. The observed acceleration of apparent inactivation of Ito after aplication of haloperidol is a typical sign of interaction with Ito-channels in the open state. Simultaneously, the negligible effect of haloperidol on the steady state inactivation curve of Ito implies no interaction with the channels in the inactivated state. However, further examination with lower haloperidol concentrations is needed in order to explain frequent ventricular dysrythmias in haloperidol-treated patients. ER -
NOVÁKOVÁ, Marie, Markéta BÉBAROVÁ, Michal PÁSEK, Peter MATEJOVIČ, Bohuslava TARABOVÁ a Lubica LACINOVÁ. Effect of sigma receptor ligand haloperidol on cardiac excitability. \textit{Physiological Research}. Praha: Inst of Physiology, Academy of Sciences, 2005, roč.~54, č.~3, s.~36P, 1 s. ISSN~0862-8408.
|