Reduction of Muscarinic K+ Channel Activity by Transferrin in Ischemic Rat Atrial Myocytes.
- Author:
Kyeong Tae PARK
1
;
Dawon KANG
;
Jaehee HAN
;
Jae Yong PARK
;
Chang Gi HUR
;
Seong Geun HONG
Author Information
1. Department of Physiology, College of Medicine and Institute of Health Sciences, Gyeongsang National University, Jinju 660-751, Korea. hong149@gsnu.ac.kr
- Publication Type:Original Article
- Keywords:
Muscarinic K+ channel;
Cardiac ischemia;
Transferrin;
Ferric iron;
Cytosolic factor
- MeSH:
Animals;
Blotting, Western;
Cytoplasm;
Cytosol;
Heart;
Muscle Cells*;
Rats*;
Transferrin*
- From:The Korean Journal of Physiology and Pharmacology
2003;7(6):333-339
- CountryRepublic of Korea
- Language:English
-
Abstract:
It has been demonstrated that an unidentified cytosolic factor (s) reduces K (ACh) channel function. Therefore, this study attempted to elucidate the cytosolic factor. Fresh cytosol isolated from normal heart (FC) depressed the K (ACh) channel activity, but cytosol isolated from the ischemic hearts (IC) did not modulate the channel function. Electrophorectic analysis revealed that a protein of ~80 kDa was markedly reduced or even lost in IC. By using peptide sequencing analysis and Western blot, this 80 kDa protein was identified as transferrin (receptor-mediated Fe3+ transporter, 76 kDa). Direct application of transferrin (100 nM) to the cytoplasmic side of inside-out patches decreased the open probability (Po, 12.7+/-6.4%, n=4) without change in mean open time (tau o, 98.5+/-1.3%, n=4). However, the equimolar apotransferrin, which is free of Fe3+, had no effect on the channel activity (N*Po, 129.1+/-13.5%, n=3). Directly applied Fe3+ (100 nM) showed results similar to those of transferrin (N*Po: 21.1+/-3.9%, n=5). However Fe2+ failed to reduce the channel function (N*Po, 106.3+/-26.8%, n=5). Interestingly, trivalent cation La (3+) inhibited N*Po of the channel (6.1+/-3.0%, n=3). Taken together, these results suggest that Fe3+ bound to transferrin can modulate the KACh channel function by its electrical property as a polyvalent cation.
