Block of L-type Ca2+ current by beauvericin, a toxic cyclopeptide, in the NG108-15 neuronal cell line.
The effects of beauverficin, a cyclodepsipeptide compound, on ion currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG108-15, were investigated with the aid of the whole-cell voltage-clamp technique. Beauvericin (0.3-100 microM) reversibly produced an inhibition of L-type voltage-dependent Ca2+ current (I(Ca,L)) in a concentration-dependent manner. Beauvericin caused no change in the overall shape of the current-voltage relationship of I(Ca,L). The IC(50) value of beauvericin-induced inhibition of I(Ca,L) was 4 microM. Neither gabapentin (30 microM) nor omega-conotoxin GVIA (3 microM) had effects on I(Ca,L). Beauvericin (30 microM) shifted the steady-state inactivation curve of I(Ca,L) to more negative membrane potentials by approximately -15 mV. The inhibitory effects of beauvericin on I(Ca,L) exhibited tonic and use-dependent characteristics. Beauvericin also suppressed I(Ca,L) evoked by repetitive action potential waveforms effectively. However, beauvericin (30 microM) had no effect on delayed rectifier K+ current in NG105-18 cells. Under current-clamp configuration, beauvericin reduced the firing frequency of action potentials. Therefore, this study indicates that beauvericin is a relatively specific inhibitor of L-type Ca2+ current in NG108-15 cells.
Wu
Sheng-Nan
SN
Department of Medical Education and Research, Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan. snwu@isca.vghks.gov.tw
Chen
Hsinyo
H
Liu
Yen-Chin
YC
Chiang
Hung-Ting
HT
D000085:Acetates / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000588:Amines; D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000633:toxicity*; D002118:Calcium / Q000737:chemistry / Q000502:physiology; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000633:toxicity*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000502:physiology; D003509:Cyclohexanecarboxylic Acids; D047630:Depsipeptides; D004594:Electrophysiology / Q000379:methods; D000077206:Gabapentin; D005910:Glioma; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000737:chemistry / Q000633:toxicity; D011188:Potassium / Q000737:chemistry / Q000502:physiology; D051381:Rats; D014407:Tumor Cells, Cultured; D005680:gamma-Aminobutyric Acid; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D000085:Acetates; D000588:Amines; D000900:Anti-Bacterial Agents; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D003509:Cyclohexanecarboxylic Acids; D047630:Depsipeptides; D010455:Peptides; C004456:beauvericin; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D020866:omega-Conotoxin GVIA; D011188:Potassium; D002118:Calcium