title: Alkalinization-induced K+ current of the mouse megakaryocyte.
abstract: We have recently found that mouse megakaryocytes responded to extracellular alkalinization to pH > 8.0, generating a K+ current under voltage-clamped conditions with the whole cell recording mode of the patch-clamp technique. The purpose of this study was to physiologically and pharmacologically characterize the alkaline-dependent K+ conductance of the megakaryocyte membrane. The alkalinization-induced K+ current (I(ALK)) did not seem to be Ca2+-dependent since I(ALK) was allowed to be generated under intracellularly Ca2+-buffered conditions with 10 mM EGTA, which completely prevented the generation of caffeine-induced Ca2+-activated currents of mouse megakaryocytes; and no [Ca2+]i elevation was evoked by the alkalinization protocol in contrast to a significant increase in [Ca2+]i in response to caffeine when [Ca2+]i was measured with a fura 2 ratiometry. I(ALK) was strongly suppressed with tetraethylammonium (TEA), 4-aminopyridine (4-AP) and streptomycin (SM), but was completely resistant to quinidine (QND). The values of IC50 for the suppression of I(ALK) with TEA, 4-AP and SM were 5.6, 0.47 and 1.5 mM, respectively. Voltage-gated K+ currents (I(K)) of the same megakaryocyte preparation were weakly suppressed with TEA and 4-AP, while they were significantly suppressed with either SM or QND. These results suggest that mouse megakaryocytes possess K+ conductance that was activated by extracellular alkalinization and that probably differs from conventional K+ conductance in its pharmacological properties.
authors.affiliation: Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Murakami
authors.forename: N
authors.initials: N
authors.lastname: Tokutomi
authors.forename: Y
authors.initials: Y
authors.lastname: Tokutomi
authors.forename: K
authors.initials: K
authors.lastname: Tomita
authors.forename: K
authors.initials: K
authors.lastname: Nishi
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004558:Electric Stimulation; D006863:Hydrogen-Ion Concentration; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D011802:Quinidine / Q000494:pharmacology; D013307:Streptomycin / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D011802:Quinidine; D002118:Calcium; D013307:Streptomycin