Responsiveness of cardiac Na+ channels to a site-directed antiserum against the cytosolic linker between domains III and IV and their sensitivity to other modifying agents |
| |
Authors: | W Beck I Benz W Bessler G Jung M Kohlhardt |
| |
Institution: | (1) Physiological Institute of the University Freiburg, Hermann-Herder-Str. 7, D-W78 Freiburg/Br., Germany;(2) Institute for Organic Chemistry of the University Tübingen, Tübingen, Germany;(3) Institute for Immunobiology of the University Freiburg, Freiburg/Br., Germany |
| |
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 -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 -subunit may not be the only target for (–)-DPI 201-106 and related compounds, if at all.This work was supported by a grant of the Deutsche Forschungs-gemeinschaft (Ko 778/2–4), Bonn. |
| |
Keywords: | Noninactivating cardiac Na+ channels Removal of inactivation Cardiac Na+ channel protein -subunit" target="_blank">gif" alt="agr" align="BASELINE" BORDER="0">-subunit |
本文献已被 SpringerLink 等数据库收录! |
|