Stimulatory effects of squamocin, an Annonaceous acetogenin, on Ca2+-activated K+ current in cultured smooth muscle cells of human coronary artery

Sheng Nan Wu, Hung Ting Chiang, Fang Rong Chang, Chih Chuang Liaw, Yang Chang Wu

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

The patch-clamp recording technique was used to investigate the effect of squamocin, an Annonaceous acetogenin, on ion currents in cultured smooth muscle cells of human coronary artery. In whole-cell configuration, squamocin (0.3-100 μM) induced Ca2+-activated K+ current [IK(ca)] in a concentration-dependent manner with an EC50 value of 4 μM. Squamocin-stimulated IK(ca) was suppressed by iberiotoxin (200 nM), paxilline (1 μM), or tetraethylammonium chloride (5 mM), yet not by apamin (200 nM) or glibenclamide (10 μM). In cells dialyzed with 10 mM EGTA, this compound had little effect on IK(ca). When cells were exposed to Ca2+-free solution, squamocin (3 μM) induced a transient increase in IK(ca). In continued presence of squamocin, an additional increase in extracellular Ca2+ (1 mM) caused a significant increase in IK(ca). Pretreatment with carbonyl cyanide m-chlorophenyl hydrazone (CCCP; 3 μM) for 5 h did not alter the magnitude of squamocin-induced IK(ca). However, squamocin (30 μM) suppressed the amplitude of voltage-dependent L-type Ca2+ current. In cell-attached configuration of single-channel recordings, squamocin applied to the bath increased the activity of large-conductance Ca2+-activated K+ (BKCa) channels without altering single-channel conductance. Conversely, in inside-out patches, squamocin applied to the intracellular surface had no effect on BKCa channel activity, whereas niflumic acid increased it effectively. These findings provide the evidence that squamocin can activate IK(Ca) in coronary arterial smooth muscle cells. Initial transient activation of IK(Ca) may reflect the squamocin-induced Ca2+ release from intracellular Ca2+ stores, whereas the sustained activation of IK(Ca) may arise from the squamocin-induced Ca2+ influx across the cell membrane. The stimulatory effect of squamocin on these channels should affect the functional activity of vascular smooth muscle cells.

Original languageEnglish
Pages (from-to)15-22
Number of pages8
JournalChemical Research in Toxicology
Volume16
Issue number1
DOIs
Publication statusPublished - 2003 Jan 1

All Science Journal Classification (ASJC) codes

  • Toxicology

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