Ceramide inhibits the outward potassium current in rat pinealocytes

In the present study, we investigated the effect of ceramide on the outward K+ current in rat pinealocytes using whole cell and single channel recordings. Three components of the whole cell outward K+ current were separated, an iberiotoxin (IBTX)‐sensitive K+ current (IKCa), a transient A current (IA) and a delayed rectifier current (IK). C6‐ceramide reduced all three components of the outward K+ current. C6‐ceramide (30 µm) caused a 53% inhibition of IKCa[a component that is generated by the IBTX‐sensitive K+ channel (BK channel)], a 27% inhibition of IA and a 17% inhibition of IK. Additional studies showed that the BK channel was not inhibited by dihydroC6‐ceramide, the inactive analog of C6‐ceramide, but mimicked by sphingomyelinase which increased intracellular ceramide. The ceramide inhibition of the BK channel was only partly dependent on its inhibition of the L‐type Ca2+ channel. Studies using specific kinase inhibitors showed that calphostin C (a protein kinase C inhibitor) and to a lesser degree lavendustin A (a tyrosine kinase inhibitor) were effective in reducing the ceramide inhibition of IKCa. Taken together, our results show that, in rat pinealocytes, ceramide reduces the outward K+ current predominantly by inhibiting IKCa. Moreover, protein kinase C appears to be the main kinase involved in the ceramide inhibition of IKCa.

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