Insensitivity of P-type calcium channels to inhalational and intravenous general anesthetics.
BACKGROUND
Voltage-gated Ca2+ channels long have been considered plausible targets for general anesthetics. Previous anesthetic studies have focused on L-, T-, or N-type channels, but there have been no studies on channels identified as P-type. Since P-type channels may be the most important voltage-gated Ca2+ channels involved in synaptic transmission in mammalian brain, it is important to establish their sensitivity to clinically relevant concentrations of general anesthetics.


METHODS
Acutely dissociated cerebellar Purkinje neurons were obtained from 7-14-day-old Sprague-Dawley rats. P-type currents were measured using the whole-cell version of the patch-clamp technique, with Ba2+ as the current carrier. General anesthetics were applied to the neurons in aqueous solution at room temperature (20-23 degrees C).


RESULTS
P-type Ca2+ channels were found to be very insensitive to a variety of general anesthetics and ethanol. Inhibitions of less than 10% were produced by 0.35 mM halothane, 0.35 mM isoflurane, 32 microM thiopental, 50 microM pentobarbital, 2 microM propofol, and 200 mM ethanol. Substantial anesthetic inhibition was found only at free aqueous concentrations much greater than those that are clinically relevant. For halothane, the dose-response curve showed an IC50 concentration of 1.17 +/- 0.02 mM and a Hill coefficient of 2.02 +/- 0.04 (mean +/- SEM).


CONCLUSIONS
The relatively small inhibitions of P-type Ca2+ channels produced by volatile and intravenous anesthetics at their free aqueous EC50 concentrations for general anesthesia in mammals suggest that these channels do not play a major role in the induction of general anesthesia.
Hall
A C
AC
Biophysics Section, Blackett Laboratory, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Lieb
W R
WR
Franks
N P
NP
D000280:Administration, Inhalation; D000768:Anesthesia, General; D000777:Anesthetics / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007275:Injections, Intravenous; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D010424:Pentobarbital / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013874:Thiopental / Q000494:pharmacology
D000777:Anesthetics; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000431:Ethanol; D007530:Isoflurane; D010424:Pentobarbital; D013874:Thiopental; D006221:Halothane; D015742:Propofol