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Electrophysiological characteristics of heart ventricular papillary muscles from histidine decarboxylase knockout and wild-type mice: effects of rosiglitazone

Background

Thiazolidinediones (troglitazone, rosiglitazone), synthetic peroxisome proliferator-activated receptor agonists, act as insulin sensitizers but beyond their antidiabetic actions improve cardiac function in experimental animals.

Aim and methods

Our first aim was to characterise the electrophysiological parameters of right ventricular papillary muscles from histidine decarboxylase knockout (HDC KO) mice compared with those of wild-type (WT) by standard microelectrode technique. Furthermore we investigated the effects of rosiglitazone (1, 3, 30 μM) on transmembrane action potentials.

Results

In KO mice statistically significant prolongation of action potential duration (APD) and decrease in maximum rate of rise of depolarisation phase (Vmax, dV/dt) can be observed. Rosiglitazone caused a concentration-dependent shortening of APD in both types of mice but reduced Vmax only in WT mice.

Conclusion

The most important difference in the electrophysiological parameters (APD, Vmax) between HDC KO and WT mice could be due to the fact that HDC KO mice are more susceptible for hyperglycaemia. The results also suggest that rosiglitazone might act on K+ channels and this effect might take part in the protective effect of rosiglitazone in ischemia/reperfusion injury observed in rats, but further, direct ionic current measurements need to support this explanation.

Acknowledgements

Supported by Grant ETT 578/2006 of the Ministry of Health.

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Correspondence to Andrea Szebeni.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Szebeni, A., Kecskeméti, V. Electrophysiological characteristics of heart ventricular papillary muscles from histidine decarboxylase knockout and wild-type mice: effects of rosiglitazone. BMC Pharmacol 7, A43 (2007). https://doi.org/10.1186/1471-2210-7-S2-A43

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  • DOI: https://doi.org/10.1186/1471-2210-7-S2-A43

Keywords

  • Rosiglitazone
  • Troglitazone
  • Action Potential Duration
  • Antidiabetic Action
  • Electrophysiological Characteristic