Jpn. J. Pharmacol. 79 (3), 343-350 (1999)


Alkalinization-Induced K+ Current of the Mouse Megakaryocyte

Makoto Murakami (1), Naofumi Tokutomi (2,*), Yoshiko Tokutomi (2), Kimio Tomita (1) and Katsuhide Nishi (2)

Departments of (1) Internal Medicine and (2) Pharmacology, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan
(*) To whom correspondence should be addressed.

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 (IALK) did not seem to be Ca2+-dependent since IALK 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. IALK 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 IALK with TEA, 4-AP and SM were 5.6, 0.47 and 1.5 mM, respectively. Voltage-gated K+ currents (IK) 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.


Keywords: Alkalinization-induced K+ current, Mouse megakaryocyte, Voltage-gated K+ current, K+ channel blocker, pH-response


Copyrightę The Japanese Pharmacological Society 1999

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