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| Content Provider | Springer Nature Link |
|---|---|
| Author | Weiss, rbert Tadmouri, Abir Mikati, Mohamad Ronjat, Michel Waard, Michel |
| Copyright Year | 2006 |
| Abstract | Direct regulation of N-type calcium channels by G-proteins is essential to control neuronal excitability and neurotransmitter release. Binding of the $${\text{G}}_{{\beta \gamma }} $$ dimer directly onto the channel is characterized by a marked current inhibition (“ON” effect), whereas the pore opening- and time-dependent dissociation of this complex from the channel produce a characteristic set of biophysical modifications (“OFF” effects). Although G-protein dissociation is linked to channel opening, the contribution of channel inactivation to G-protein regulation has been poorly studied. Here, the role of channel inactivation was assessed by examining time-dependent G-protein de-inhibition of Cav2.2 channels in the presence of various inactivation-altering β subunit constructs. G-protein activation was produced via μ-opioid receptor activation using the DAMGO agonist. Whereas the “ON” effect of G-protein regulation is independent of the type of β subunit, the “OFF” effects were critically affected by channel inactivation. Channel inactivation acts as a synergistic factor to channel activation for the speed of G-protein dissociation. However, fast inactivating channels also reduce the temporal window of opportunity for G-protein dissociation, resulting in a reduced extent of current recovery, whereas slow inactivating channels undergo a far more complete recovery from inhibition. Taken together, these results provide novel insights on the role of channel inactivation in N-type channel regulation by G-proteins and contribute to the understanding of the physiological consequence of channel inactivation in the modulation of synaptic activity by G-protein coupled receptors. |
| Starting Page | 115 |
| Ending Page | 129 |
| Page Count | 15 |
| File Format | |
| ISSN | 00316768 |
| Journal | Pflügers Archiv |
| Volume Number | 454 |
| Issue Number | 1 |
| e-ISSN | 14322013 |
| Language | English |
| Publisher | Springer-Verlag |
| Publisher Date | 2006-12-14 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | N-type calcium channel Cav2.2 subunit G-protein G-protein coupled receptor μ-opioid receptor inactivation β subunit Human Physiology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Physiology Physiology (medical) Clinical Biochemistry |
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