Ceramide inhibits the inwardly rectifying potassium current in GH(3) lactotrophs.
The effects of ceramide on ion currents in rat pituitary GH(3) cells were investigated. Hyperpolarization-elicited K(+) currents present in GH(3) cells were studied to determine the effect of ceramide and other related compounds on the inwardly rectifying K(+) current (I(K(IR))). Ceramide (C(2)-ceramide) suppressed the amplitude of I(K(IR)) in a concentration-dependent manner, with an IC(50) value of 5 microM. Ceramide caused a rightward shift in the midpoint for the activation curve of I(K(IR)). Pretreatment with PD-98059 (30 microM) or U-0126 (30 microM) did not prevent ceramide-mediated inhibition of I(K(IR)). However, the magnitude of ceramide-induced inhibition of I(K(IR)) was attenuated in GH(3) cells preincubated with dithiothreitol (10 microM). TNF alpha (100 ng/g) also suppressed I(K(IR)). In the inside-out configuration, application of ceramide (30 microM) to the bath slightly suppressed the activity of large conductance Ca(2+)-activated K(+) channels. Under the current clamp mode, ceramide (10 microM) increased the firing of action potentials. Cells that exhibited an irregular firing pattern were converted to those displaying a regular firing pattern after application of ceramide (10 microM). Ceramide also suppressed I(K(IR)) in neuroblastoma IMR-32 cells. Therefore, ceramide can produce a depressant effect on I(K(IR)). The blockade of this current by ceramide may affect cell function.
Wu
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Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan, Republic of China. snwu@isca.vghks.gov.tw
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Kuo
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Chiang
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D002518:Ceramides / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D009570:Nitriles / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000502:physiology; D011388:Prolactin / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured
D002070:Butadienes; D020746:Calcium Channels, L-Type; D002518:Ceramides; D016207:Cytokines; D004791:Enzyme Inhibitors; D005419:Flavonoids; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009570:Nitriles; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; C113580:U 0126; D011388:Prolactin; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D002118:Calcium; D004229:Dithiothreitol