1998 Fiscal Year Final Research Report Summary
Regulation of L-type Ca channel and phosphorylation
| Project/Area Number |
09670044
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
YAMAOKA Kaoru Hiroshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10200586)
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| Project Period (FY) |
1997 – 1998
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| Keywords | L-type Ca channel / magnesium / calcium / phosphorylation / cardiac myocyte / cysteine / dorsal root ganglion / bull-frog |
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| Research Abstract |
The role of intracellular Mg^<2+> in the regulation of L-type Ca channel through A-kinase phosphorylation was elucidated using frog ventricular myocytes. When concentration of intracellular Mg^<2+> was lowered beyond a physiological level, it enhanced L-type Ca channel current (I_<Ca.L>) remarkably due to unblock of the channel from Mg^<2+>. The channel becomes insensitive to Mg^<2+> block when cell was phosphorylated through A-kinase stimulation. It concludes that phosphorylation regulates L-type Ca channel in cardiac myocytes through charging sensitivity to Mg^<2+> block. This particular type of Mg^<2+> block was not found in L-type Ca channel in frog dorsal root ganglion (DRG) neurons. The absence of Mg^<2+> block well correlates to the absence of the regulation through A-kinase in L-type Ca channel of frog DRG neurons. I have further found that membrane impermeable methanethiosulfonate compounds (MTS) that modify SH residues of cysteine can increase I_<Ca> dramatically from the intracellular side. This enhancing effect was not seen when I_<Ca> was pre-conditionally increased to a sub-maximal level by A-kinase stimulation. This indicates that MTS reagents affect one of the regulatory steps of phosphorylation mechanism. These results indicate that we may gain a further step to understand the mechanism of phosphorylation pathway if we target cysteines of intracellular region of L-type Ca channel or its associated proteins.
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