Decreasing expression of α1C calcium L-type channel subunit mRNA in rat ventricular myocytes upon manganese exposure
✍ Scribed by Huijuan Yang; Tiannan Wang; Jieyue Li; Ling Gu; Xiaoxiang Zheng
- Publisher
- John Wiley and Sons
- Year
- 2006
- Tongue
- English
- Weight
- 181 KB
- Volume
- 20
- Category
- Article
- ISSN
- 1095-6670
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✦ Synopsis
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 M Mn 2+ and 100 M 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 realtime 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.