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Decreasing expression of α 1C calcium L‐type channel subunit mRNA in rat ventricular myocytes upon manganese exposure
Author(s) -
Yang Huijuan,
Wang Tiannan,
Li Jieyue,
Gu Ling,
Zheng Xiaoxiang
Publication year - 2006
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.20133
Subject(s) - manganese , chemistry , calcium , calcium channel , l type calcium channel , myocyte , biophysics , voltage dependent calcium channel , patch clamp , protein subunit , messenger rna , endocrinology , microbiology and biotechnology , biochemistry , biology , receptor , organic chemistry , gene
Manganese is an essential trace element found in many enzymes. As it is the case of many essential trace elements, excessive level of manganese is toxic. It has been proven that excessive manganese could cause heart problems. In order to understand the mechanism of manganese toxicity in the heart, the effects of manganese on isolated rat ventricular myocytes were studied. The L‐type calcium channel current was measured by whole‐cell patch clamp recording mode. In the electrophysiology experiments, both 50 μM Mn 2+ and 100 μM Mn 2+ could effectively decrease the channel current amplitude density by 35.7% and 68.2%, respectively. Moreover, Mn 2+ shifted the steady‐state activation curve toward more positive potential and the steady‐state inactivation curve toward more negative potential. Investigation by RT‐PCR showed that the mRNA expression of α 1C /Cav1.2 treated with manganese was decreased depending on its concentration, while the mRNA expression of α 1D /Cav1.3 was almost unchanged. Fluo‐3/AM was utilized for real‐time free calcium scanning with laser scanning confocal microscopy (LSCM), and the results showed that Mn 2+ could elicit a slow and continuous increase of [Ca 2+ ] i in a concentration‐dependent manner. These results have suggested that manganese could interfere with the function of the L‐type calcium channel, downregulate the mRNA expression of α 1C /Cav1.2, and thus causing long‐lasting molecular changes of L‐type calcium channel which have probably been triggered by overloading of calcium in myocytes. © 2006 Wiley Periodicals, Inc. J Biochem Mol Toxicol 20:159–166, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/jbt.20133