Ethanol reduces the duration of single evoked spikes by a selective inhibition of voltage-gated calcium currents in acutely dissociated supraoptic neurons of the rat.
The effects of ethanol were studied on single evoked spikes recorded at 20 degrees C with the perforated-patch method in acutely dissociated rat supraoptic neurons. In seven out of eight neurons, ethanol (50 mM) significantly reduced the spike duration by selectively decreasing the decay time (82+/-2% of the control), leaving the amplitude and rise time unaffected. Resting potential and threshold did not change. Similarly, CdCl2 at a concentration of 100 microM, which blocks all voltage-activated calcium current in the supraoptic neurons, reduced the decay time of single evoked spikes (76+/-3% of the control, n=10) without modifying the other above-mentioned parameters. In addition, exposure to 100 microM CdCl2 prevented any subsequent effect of 50 mM ethanol (n = 5). Exposure to apamin (10 nM) and iberiotoxin (10 nM) did not have any effect on single evoked spikes. Because these concentrations are effective in blocking, respectively, small (SK) and large (BK) conductance calcium-dependent potassium channels in these neurons, this result shows that these currents are not involved in either the shaping of single evoked spikes or the actions of ethanol on spike shape. The sustained component of whole-cell recorded calcium current measured at -10 mV (hp -60 mV) was inhibited by ethanol in a dose-dependent manner, with a significant effect detectable at 25 mM. Exposure to 50 mM ethanol significantly reduced the sustained current to 70+/-5% of the control (n=12), without any apparent shift of the current-voltage relationship. Control exposure of the neurons to either 50 mM urea or 50 mM sucrose did not affect the voltage-gated calcium currents. We conclude that ethanol reduces the duration of single evoked spikes by a specific inhibition of voltage-activated calcium currents. The results suggest that, in addition to its direct effects on release of vasopressin and oxytocin from neurohypophysial terminals, ethanol could also affect hormonal release via changes in firing patterns arising in the cell bodies.
Widmer
H
H
Department of Pharmacology and Molecular Toxicology, University of Massachussets Medical Center, Worcester 06104, USA.
Lemos
J R
JR
Treistman
S N
SN
D000818:Animals; D015220:Calcium Channels / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects*; D015640:Ion Channel Gating; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013495:Supraoptic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D015220:Calcium Channels; D000431:Ethanol