Luo, An-tao, Luo, Hong-yan, Hu, Xin-wu, Gao, Lin-lin, Liang, Hua-min, Tang, Ming and Hescheler, Juergen (2010). Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C. Acta Pharmacol. Sin., 31 (11). S. 1438 - 1447. SHANGHAI: ACTA PHARMACOLOGICA SINICA. ISSN 1745-7254

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Abstract

Aim: To study the effects and mechanisms by which hyposmotic challenge modulate function of L-type calcium current (I-Ca,I-L) in rat ventricular myocytes. Methods: The whole-cell patch-clamp techniques were used to record I-Ca,I-L in rat ventricular myocytes. Results: Hyposmotic challenge(similar to 220 mosmol/L) induced biphasic changes of I-Ca,I-L, a transient increase followed by a sustained decrease. I-Ca,I-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 I-Ca,I-L to 78.1%+/- 11.0% of control, caused the inactivation of I-Ca,I-L, and shifted the steady-state inactivation curve of I-Ca,I-L to the right. The decreased I-Ca,I-L induced by hyposmotic swelling was reversed by isoproterenol or protein kinase A (PKA) activator foskolin. Hyposmotic swelling also reduced the stimulated I-Ca,I-L by isoproterenol or foskolin. PKA inhibitor H-89 abolished swelling-induced transient increase of I-Ca,I-L, but did not affect the swelling-induced sustained decrease of I-Ca,I-L. NO donor SNAP and protein kinase G (PKG) inhibitor Rp-8-Br-PET-cGMPS did not interfere with swelling-induced biphasic changes of I-Ca,I-L. Protein kinase C (PKC) activator PMA decreased I-Ca,I-L and hyposmotic solution with PMA reverted the decreased I-Ca,I-L by PMA. PKC inhibitor BIM prevented the swelling-induced biphasic changes of I-Ca,I-L. Conclusion: Hyposmotic challenge induced biphasic changes of I-Ca,I-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 I-Ca,I-L during short exposure to hyposmotic solution.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Luo, An-taoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luo, Hong-yanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hu, Xin-wuUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gao, Lin-linUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Liang, Hua-minUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tang, MingUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-492800
DOI: 10.1038/aps.2010.112
Journal or Publication Title: Acta Pharmacol. Sin.
Volume: 31
Number: 11
Page Range: S. 1438 - 1447
Date: 2010
Publisher: ACTA PHARMACOLOGICA SINICA
Place of Publication: SHANGHAI
ISSN: 1745-7254
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MYOCARDIAL-ISCHEMIA; CARDIAC MYOCYTES; CA2+ CHANNELS; CELL-VOLUME; REPERFUSION; MECHANISMS; CURRENTS; HEART; CARDIOMYOCYTES; ENHANCEMENTMultiple languages
Chemistry, Multidisciplinary; Pharmacology & PharmacyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/49280

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