Halothane inhibits hyperpolarization and potassium channels in human red blood cells.
The effect of halothane on the Ca2+-sensitive K+ channel in human erythrocytes has been investigated. The red cells were suspended in buffer-free salt solutions containing Ca2+ or 45Ca2+. The protonophore CCCP was added to bring about a rapid equilibration of protons across the plasma membrane. After addition of the divalent cation ionophore A23187, the cells took up Ca2+ and this caused the K+ channels to open. When the medium contained 1 mM K+, the addition of A23187 induced a transient hyperpolarization of the cells, as monitored by measurement of the pH of the medium. The cellular pH, being buffered by haemoglobin, was virtually constant. Halothane reversibly inhibited hyperpolarization and limited the release of cellular K+ in a dose-dependent way, but did not inhibit the Ca2+-transporting properties of A23187. No stimulatory effects of halothane were observed even at low halothane concentrations. In conclusion, halothane reversibly inhibits the Ca2+-sensitive K+ channel in human erythrocytes with an ED50 of about 0.5 mM.
Scharff
O
O
Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen, Denmark.
Foder
B
B
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D001834:Body Water / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000494:pharmacology; D002132:Calcium Radioisotopes; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006221:Halothane / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D015221:Potassium Channels / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology; D012965:Sodium Chloride / Q000494:pharmacology
D002132:Calcium Radioisotopes; D015221:Potassium Channels; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000001:Calcimycin; D012965:Sodium Chloride; D011189:Potassium Chloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002118:Calcium; D006221:Halothane