Linked Life Data

9037754

Source:http://linkedlifedata.com/resource/pubmed/id/9037754

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1997-3-21
pubmed:abstractText
Failure of inactivation is the typical response of voltage-gated Na+ channels to the cytosolic presence of proteolytic enzymes, protein reagents such as N-bromoacetamide (NBA) or iodate, and antibodies directed against the linker between domains III and IV of the alpha-subunit. The present patch clamp experiments with cardiac Na+ channels aimed to test the hypothesis that these interventions may provoke the occurrence of non-inactivating Na+ channels with distinct kinetic properties. A site-directed polyclonal antibody (anti-SLP2, target sequence 1481-1496 of the cardiac Na+ channel alpha-subunit) eliminated fast Na+ inactivation to induce burst activity which was accompanied by the occurrence of two open states. A deactivation process terminated channel activity during membrane depolarization proceeding with time constants of close to 40 ms (at -40 mV). NBA-modified and iodatemodified Na+ channels were kinetically indistinguishable from the anti-SLP2-modified type since they likewise deactivate and, thus, attain an only moderate Po of close to 20%. This is fundamentally different from the behaviour of enzymatically-modified Na+ channels: after cytosolic proteolysis with alpha-chymotrypsin, trypsin or pronase, mean Po during membrane depolarization amounted to approximately 40% because deactivation operated extremely slowly and less efficiently (time constants 100-200 ms at -40 mV, as a minimum) or was virtually non-operating. Invitro cleavage of the synthetic linker sequence 1481-1496 confirmed that this part of the alpha-subunit provides a substrate for these peptidases or reactants for NBA but cannot be chemically modified by iodate. This iodate resistance indicates that iodate-modified Na+ channels are based on a structural alteration of still another region which is also involved in Na+ inactivation, besides the linker between domains III and IV of the alpha-subunit. Endogenous peptidases such as calpain did not affect Na+ inactivation. This stresses the stochastic nature of a kinetic peculiarity of cardiac Na+ channels, mode-switching to a non-inactivating mode.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0175-7571
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
189-200
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9037754-Acetamides, pubmed-meshheading:9037754-Amino Acid Sequence, pubmed-meshheading:9037754-Animals, pubmed-meshheading:9037754-Antibodies, pubmed-meshheading:9037754-Calpain, pubmed-meshheading:9037754-Cytosol, pubmed-meshheading:9037754-Heart, pubmed-meshheading:9037754-Iodates, pubmed-meshheading:9037754-Ion Channel Gating, pubmed-meshheading:9037754-Macromolecular Substances, pubmed-meshheading:9037754-Membrane Potentials, pubmed-meshheading:9037754-Molecular Sequence Data, pubmed-meshheading:9037754-Peptide Hydrolases, pubmed-meshheading:9037754-Protein Structure, Secondary, pubmed-meshheading:9037754-Sensitivity and Specificity, pubmed-meshheading:9037754-Sodium, pubmed-meshheading:9037754-Sodium Channels, pubmed-meshheading:9037754-Structure-Activity Relationship
pubmed:year
1997
pubmed:articleTitle
Two types of modified cardiac Na+ channels after cytosolic interventions at the alpha-subunit capable of removing Na+ inactivation.
pubmed:affiliation
Physiological Institute University of Freiburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't