title: The inhibitory effect of Ca2+-activated K+ channel activator, BMS on L-type Ca2+ channels in rat ventricular myocytes.
abstract: OBJECTIVE
  We investigated the effects of BMS-204352 (BMS), a big-conductance calcium-activated potassium (BK(Ca)) channel activator, on L-type Ca(2+) channels.
  
  
  METHODS
  Electrophysiological recordings were performed in isolated rat ventricular myocytes. Whole-cell configuration was used.
  
  
  RESULTS
  BMS caused inhibition of the Ca(2+) current in a dose-dependent manner, with K(d) of 6.00 ± 0.67 μM and a Hill coefficient of 1.33 ± 0.18. BMS did not affect the steady-state activation of L-type Ca(2+) channels. However, for those in steady-state inactivation, BMS shifted the half-maximal potential (V(1/2)) by -11 mV, but the slope value (k) was not altered. Iberiotoxin, inhibitor of membrane BK(Ca) channels and paxilline, inhibitor of mitochondrial BK(Ca) channel did not affect the inhibitory effect of BMS on L-type Ca(2+) channels. Pretreatment with inhibitors of protein kinase A (PKA), protein kinase C (PKC), and protein kinase G (PKG) did not significantly alter the inhibitory effect of BMS on L-type Ca(2+) current. The presence of a selective β-adrenergic receptor agonist, isoproterenol did not affect the inhibitory effect of BMS on L-type Ca(2+) current. Based on these results, we concluded that the inhibition of L-type Ca(2+) channels by BMS is independent of the inhibition of BK(Ca) channels or intracellular signaling pathways.
  
  
  CONCLUSIONS
  It is important to take BMS-204352 (BMS) effects on L-type Ca(2+) channels into consideration when using BMS as a BK(Ca) channel activator or therapeutic target in ventricular myocytes.
authors.affiliation: Department of Physiology, Kangwon National University School of Medicine, Chuncheon, 200-701, Republic of Korea.
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Seong Woo
authors.initials: SW
authors.lastname: Choi
authors.forename: Won-Kyo
authors.initials: WK
authors.lastname: Jung
authors.forename: Su-Hyun
authors.initials: SH
authors.lastname: Jo
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Il-Whan
authors.initials: IW
authors.lastname: Choi
authors.forename: Jeong-Im
authors.initials: JI
authors.lastname: Sin
authors.forename: Eun Bo
authors.initials: EB
authors.lastname: Shim
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C424388:BMS204352; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D007211:Indoles; D024681:Potassium Channels, Calcium-Activated