Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA065

Poster Communications

Investigation role of Urotensin II on electrical activity of ventricular myocytes

H. S. Al Ali1, G. Rodrigo1, D. Lambert1

1. Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom.

Evidence from studies on patients with heart failure show that a reduction in contractile function is associated with changes in Ca2+ regulation (Houser et al. 2000). Furthermore, levels of Urotensin II (UII) are elevated in the plasma of patients with heart failure (Ng et al 2002), and it is suggested that this may lead to myocardial dysfunction. Our previous work has shown that UII reduces contraction strength of adult rat ventricular myocytes (ARVMs) and this reflects a reduction in systolic calcium (Al Ali et al. 2018). The aim of this study is to investigate the effect of UII on the action potential and L-type calcium currents (LTCC) in ventricular myocytes. ARVMs were isolated via enzymatic digestion of adult Wistar rat hearts. Electrical activity was recorded from freshly isolated ARVMs. Action potentials (AP) were recorded using the whole cell patch clamp technique with high resistance pipettes (12-15MΩ). LTCC was recorded using low resistance pipettes (2-4MΩ), filled with an electrode solution containing 10mM BAPTA. To investigate the effects of UII on electrical activity of the heart, the percentage change in action potential duration (APD30/50/90) was calculated in freshly isolated ARVMs in response to an acute application of UII (200nM for10 mins). The data show UII reduced APD30 from 9.5 ± 1.4 ms in normal Tyrode (NT) to 5.3 ± 0.9 ms in UII (p<0.01) and APD50 from 19.5 ± 2.1 ms in NT to 12.1 ± 1.6 ms in UII (p<0.001). However, there was no significant change in APD90 between UII at 57.2 ± 5.2 ms in NT versus 50.9 ± 6.0 ms in UII (p>0.05, ns; n= 6 hearts; 41 cells). We set out to investigate the effect of UII on the LTCC, which is suggested by the reduction in APD50. The data show that UII (200nM) decreased the LTCC recorded from ARVMs at 0mV from 14.7 ± 0.6 pA/pF in NT to 12.6 ± 0.7 pA/pF in UII (n= 4 cells p<0.001). The data show a reduction in APD30/50 and LTCC in response to acute application of UII in ventricular myocytes, which may contribute to the reduction in contraction strength.

Where applicable, experiments conform with Society ethical requirements