Effects in Yasni Exposé of Sheng-Nan Wu

(191 since 28.01.2012)


Country: Republic of China (Taiwan), Language: English
Sheng-Nan Wu @ Dept Physiol, Natl Cheng Kung U Med Coll, Tainan City

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Sheng-Nan Wu @ Tainan City
Jan 12  +

6 results for Sheng-Nan Wu

Evidence for Mitoxantrone-induced Block of Inwardly Rectifying K+ Channels Expressed in the Osteoclast Precursor RAW 264.7 Cells Differentiated with Lipopolysaccharide

Background/Aims: Mitoxanthrone (MX) is an anthracenedione antineoplastic agent. Whether this drug and other related compounds have any effects on ion currents in osteoclasts remains largely unclear. Methods: In this study, the effects of MX and other related compounds on inwardly rectifying K+ current (IK(IR)) were investigated in RAW 264.7 osteoclast precursor cells treated with lipopolysaccharide. Results: The IK(IR) in these cells are blocked by BaCl2 (1 mM). MX (1-100 µM) decreased the amplitude of IK(IR) in a concentration-dependent manner with an IC50 value of 6.4 µM. MX also slowed the time course of IK(IR) inactivation elicited by large hyperpolarization. Doxorubicin (10 µM), 17β-estradiol (10 µM) and tertiapin (1 µM) decreased the IK(IR) amplitude in these cells. In bafilomycin A1-treated cells, MX-mediated block of IK(IR) still existed. In cell-attached configuration, when the electrode was filled with MX (10 µM), the activity of inwardly rectifying K+ (Kir) channels was decreased with no change in single-channel conductance. MX-mediated reduction of channel activity is accompanied by a shortening of mean open time. Under current-clamp conditions, addition of MX resulted in membrane depolarization. Therefore, MX can interact with the Kir channels to decrease amplitude and to depolarize the membrane in these cells. Conclusion: The block by the IK(IR)this drug of Kir2.1 channels appears to be one of the important mechanisms underlying its actions on the resorptive activity of osteoclasts, if similar results occur in vivo. Targeting at Kir channels may be clinically useful as an adjunctive regimen to anti-cancer drugs (e.g., MX or doxorubicin) in influencing the resorptive activity of osteoclasts.
Sheng-Nan Wu @ Tainan City
content.karger.com 2012-08-04  +  

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