ISSN:
1432-1424
Keywords:
Noninactivating cardiac Na+ channels
;
Removal of inactivation
;
Cardiac Na+ channel protein
;
α-subunit
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Chemistry and Pharmacology
Notes:
Abstract Elementary Na+ currents were recorded in inside-out patches from neonatal rat heart cardiocytes to analyze the influence of a site-directed polyclonal anti-serum against the linker region between the domains III and IV (amino acids 1489–1507 of the cardiac Na+ channel protein) on Na+ channel gating and to test whether this part of the α-subunit may be considered as a target for modifying agents such as the (−)-enantiomer of DPI 201-106. Anti-SLP 1 serum (directed against amino acids 1490–1507) evoked, usually within 10–15 min after cytosolic administration, modified Na+ channel activity. Antiserum-modified Na+ channels retain a single open state but leave, at −60 mV for example, their conducting configuration consistently with an about threefold lower rate than normal Na+ channels. Another outstanding property of noninactivating Na+ channels, enhanced burst activity, may be quite individually pronounced, a surprising result which is difficult to interpret in terms of structure function relations. Removal of inactivation led to an increase of reconstructed peak I Na (indicating a rise in NP o) and changed I Na decay to obey second-order kinetics, i.e., open probability declined slowly but progressively during membrane depolarization. The underlying deactivation process is voltage dependent and responds to a positive voltage shift with a deceleration but may operate even at the same membrane potential with different rates. Iodatemodified Na+ channels exhibit very similar properties including a conserved conductance. They are likewise controlled by an efficient, voltage-dependent deactivation process. Modification by (−)-DPI 201-106 fundamentally contrasts to the influence of anti-SLP 1 serum and the protein reagent iodate since (−)-DPI-modified Na+ channels maintain their open probability for at least 120 msec, i.e., a deactivation process seems lacking. This functional difference suggests that the linker region between the domains III and IV of the α-subunit may not be the only target for (−)-DPI 201-106 and related compounds, if at all.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00234504
