Hydrogen peroxide inhibits chloride channels of the sarcoplasmic reticulum of skeletal muscle
| dc.contributor.author | Kourie, Joseph | |
| dc.date.accessioned | 2015-12-13T23:22:40Z | |
| dc.date.issued | 1999 | |
| dc.date.updated | 2015-12-12T09:11:57Z | |
| dc.description.abstract | Data obtained with the lipid bilayer technique indicate that cis (cytoplasmic) concentration of 4.4-22 mm hydrogen peroxide (H2O2), is a water-soluble oxidant. [H2O2](cis) (n = 26) reversibly inhibits the multisubconductance SCl channel of the sarcoplasmic reticulum vesicles from rabbit skeletal muscle. At -40 mV, the mean values of the current amplitude (I) and the probability of the SCl channel being open (P(0)) were reduced significantly (n = 8) from -6.14 ± 0.42 pA and 0.69 ± 0.06 (for all conductance levels) in control 0.0 mM [H2O2](cis) to -1.10 ± 0.51 pA and 0.13 ± 0.04 (for the intermediate subconductance states) in 8.8 mu [H2O2](cis), respectively. The [H2O2](cis)-induced decrease in P(o) is mainly due to a decrease in the mean open time T(o). The mechanism of [H2O2](cis) effects on the multiconductance SCl channel is characterized by a mode shift in the channel state from the main conductance state to the low subconductance states. The estimated concentration of the [H2O2](cis) for the half inhibitory constant, K(i), was 11.78 mm, higher than the estimated 8.0 and 8.1 mm for the parameters P(o) and T(o), respectively; indicating that the conductance of the SCl channel is less sensitive than the gating kinetics of the channel. After a lag period of between 30 to 60 sec, the lipophilic SH-oxidizing agent 4,4'-dithiodipyridine (4,4'-DTDP) added to the cis side at 1.0 mu removed the inhibitory effects of 8.8 mu [H2O2](cis). The 4,4'-DTDP-enhanced SCl channel activity was blocked after the addition of 0.5 mM ATP to the cis side of the channel. The addition of 1.0 mu 4,4'-DTDP to the cis or trans solutions facing an SCl channel already subjected to 0.5 mu [ATP](cis) or [ATP](trans) failed to activate the ATP-inhibited SCl channel. These findings suggest that 4,4'-DTDP is not preventing the binding of ATP to its binding site on the channel protein. The interaction of H2O2 with the SCl channel proteins is consistent with a thiol-disulfide redox state model for regulating ion transport, where SH groups can directly modify the function of the channel and/or the availability of regulatory sites on the channel proteins. The H2O2 effects on the Ca2+ countercurrent through the SCl channel are also consistent with H2O2-modification of the mechanisms involved in the Ca2+ regulation, which underlies excitation- contraction coupling in skeletal muscle. | |
| dc.identifier.issn | 0022-2631 | |
| dc.identifier.uri | http://hdl.handle.net/1885/91558 | |
| dc.publisher | Springer | |
| dc.source | Journal of Membrane Biology | |
| dc.subject | Keywords: chloride channel; animal tissue; article; binding site; calcium current; excitation contraction coupling; ion transport; lipid bilayer; membrane conductance; nonhuman; sarcoplasmic reticulum; skeletal muscle; Adenosine Triphosphate; Animals; Chloride Chan ATP-sensitive channels; Bilayer technique; Calcium countercurrent; Reactive oxygen species; Sulfhydryl group (SH)-oxidizing and SH-reducing agents | |
| dc.title | Hydrogen peroxide inhibits chloride channels of the sarcoplasmic reticulum of skeletal muscle | |
| dc.type | Journal article | |
| local.bibliographicCitation.lastpage | 36 | |
| local.bibliographicCitation.startpage | 25 | |
| local.contributor.affiliation | Kourie, Joseph, College of Physical and Mathematical Sciences, ANU | |
| local.contributor.authoremail | repository.admin@anu.edu.au | |
| local.contributor.authoruid | Kourie, Joseph, u9111360 | |
| local.description.embargo | 2037-12-31 | |
| local.description.notes | Imported from ARIES | |
| local.description.refereed | Yes | |
| local.identifier.absfor | 030499 - Medicinal and Biomolecular Chemistry not elsewhere classified | |
| local.identifier.ariespublication | MigratedxPub22339 | |
| local.identifier.citationvolume | 172 | |
| local.identifier.doi | 10.1007/s002329900580 | |
| local.identifier.scopusID | 2-s2.0-0032706288 | |
| local.identifier.uidSubmittedBy | Migrated | |
| local.type.status | Published Version |
Downloads
Original bundle
1 - 1 of 1
No Thumbnail Available
- Name:
- 01_Kourie_Hydrogen_peroxide_inhibits_1999.pdf
- Size:
- 1.11 MB
- Format:
- Adobe Portable Document Format