@article{APS4090,
author = {An-tao Luo and Hong-yan Luo and Xin-wu Hu and Lin-lin Gao and Hua-min Liang and Ming Tang and Jürgen Hescheler},
title = {Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C},
journal = {Acta Pharmacologica Sinica},
volume = {31},
number = {11},
year = {2016},
keywords = {},
abstract = {Aim: To study the effects and mechanisms by which hyposmotic challenge modulate function of L-type calcium current (ICa,L) in rat ventricular myocytes.
Methods: The whole-cell patch-clamp techniques were used to record ICa,L in rat ventricular myocytes.
Results: Hyposmotic challenge(~220 mosmol/L) induced biphasic changes of ICa,L, a transient increase followed by a sustained decrease. ICa,L increased by 19.1%±6.1% after short exposure (within 3 min) to hyposmotic solution. On the contrary, long hyposmotic challenge (10 min) decreased ICa,L to 78.1%±11.0% of control, caused the inactivation of ICa,L, and shifted the steady-state inactivation curve of ICa,L to the right. The decreased ICa,L induced by hyposmotic swelling was reversed by isoproterenol or protein kinase A (PKA) activator foskolin. Hyposmotic swelling also reduced the stimulated ICa,L by isoproterenol or foskolin. PKA inhibitor H-89 abolished swelling-induced transient increase of ICa,L, but did not affect the swelling-induced sustained decrease of ICa,L. NO donor SNAP and protein kinase G (PKG) inhibitor Rp-8-Br-PET-cGMPS did not interfere with swelling-induced biphasic changes of ICa,L. Protein kinase C (PKC) activator PMA decreased ICa,L and hyposmotic solution with PMA reverted the decreased ICa,L by PMA. PKC inhibitor BIM prevented the swelling-induced biphasic changes of ICa,L.
Conclusion: Hyposmotic challenge induced biphasic changes of ICa,L, a transient increase followed by a sustained decrease, in rat ventricular myocytes through PKC pathway, but not PKG pathway. PKA system could be responsible for the transient increase of ICa,L during short exposure to hyposmotic solution.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/4090}
}