Tags

Type your tag names separated by a space and hit enter

Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes.
Eur J Pharmacol. 2013 Jun 15; 710(1-3):10-9.EJ

Abstract

Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations.

Authors+Show Affiliations

Department of Physiology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23588116

Citation

Kistamás, Kornél, et al. "Effects of Pioglitazone On Cardiac Ion Currents and Action Potential Morphology in Canine Ventricular Myocytes." European Journal of Pharmacology, vol. 710, no. 1-3, 2013, pp. 10-9.
Kistamás K, Szentandrássy N, Hegyi B, et al. Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes. Eur J Pharmacol. 2013;710(1-3):10-9.
Kistamás, K., Szentandrássy, N., Hegyi, B., Ruzsnavszky, F., Váczi, K., Bárándi, L., Horváth, B., Szebeni, A., Magyar, J., Bányász, T., Kecskeméti, V., & Nánási, P. P. (2013). Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes. European Journal of Pharmacology, 710(1-3), 10-9. https://doi.org/10.1016/j.ejphar.2013.03.047
Kistamás K, et al. Effects of Pioglitazone On Cardiac Ion Currents and Action Potential Morphology in Canine Ventricular Myocytes. Eur J Pharmacol. 2013 Jun 15;710(1-3):10-9. PubMed PMID: 23588116.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of pioglitazone on cardiac ion currents and action potential morphology in canine ventricular myocytes. AU - Kistamás,Kornél, AU - Szentandrássy,Norbert, AU - Hegyi,Bence, AU - Ruzsnavszky,Ferenc, AU - Váczi,Krisztina, AU - Bárándi,László, AU - Horváth,Balázs, AU - Szebeni,Andrea, AU - Magyar,János, AU - Bányász,Tamás, AU - Kecskeméti,Valéria, AU - Nánási,Péter P, Y1 - 2013/04/12/ PY - 2012/11/20/received PY - 2013/03/21/revised PY - 2013/03/28/accepted PY - 2013/4/17/entrez PY - 2013/4/17/pubmed PY - 2014/1/18/medline SP - 10 EP - 9 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 710 IS - 1-3 N2 - Despite its widespread therapeutical use there is little information on the cellular cardiac effects of the antidiabetic drug pioglitazone in larger mammals. In the present study, therefore, the concentration-dependent effects of pioglitazone on ion currents and action potential configuration were studied in isolated canine ventricular myocytes using standard microelectrode, conventional whole cell patch clamp, and action potential voltage clamp techniques. Pioglitazone decreased the maximum velocity of depolarization and the amplitude of phase-1 repolarization at concentrations ≥3 μM. Action potentials were shortened by pioglitazone at concentrations ≥10 μM, which effect was accompanied with significant reduction of beat-to-beat variability of action potential duration. Several transmembrane ion currents, including the transient outward K(+) current (Ito), the L-type Ca(2+) current (ICa), the rapid and slow components of the delayed rectifier K(+) current (IKr and IKs, respectively), and the inward rectifier K(+) current (IK1) were inhibited by pioglitazone under conventional voltage clamp conditions. Ito was blocked significantly at concentrations ≥3 μM, ICa, IKr, IKs at concentrations ≥10 μM, while IK1 at concentrations ≥30 μM. Suppression of Ito, ICa, IKr, and IK1 has been confirmed also under action potential voltage clamp conditions. ATP-sensitive K(+) current, when activated by lemakalim, was effectively blocked by pioglitazone. Accordingly, action potentials were prolonged by 10 μM pioglitazone when the drug was applied in the presence of lemakalim. All these effects developed rapidly and were readily reversible upon washout. In conclusion, pioglitazone seems to be a harmless agent at usual therapeutic concentrations. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/23588116/Effects_of_pioglitazone_on_cardiac_ion_currents_and_action_potential_morphology_in_canine_ventricular_myocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(13)00284-7 DB - PRIME DP - Unbound Medicine ER -