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Ceramide inhibits the outward potassium current in rat pinealocytes
Author(s) -
Chik C. L.,
Li B.,
Karpinski E.,
Ho A. K.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00566.x
Subject(s) - ceramide , iberiotoxin , lipid signaling , microbiology and biotechnology , biology , chemistry , tyrosine kinase , potassium channel , endocrinology , medicine , biochemistry , signal transduction , apoptosis , receptor
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 ( I KCa ), a transient A current ( I A ) and a delayed rectifier current ( I K ). C6‐ceramide reduced all three components of the outward K + current. C6‐ceramide (30 µ m ) caused a 53% inhibition of I KCa [a component that is generated by the IBTX‐sensitive K + channel (BK channel)], a 27% inhibition of I A and a 17% inhibition of I K . 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 Ca 2+ 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 I KCa . Taken together, our results show that, in rat pinealocytes, ceramide reduces the outward K + current predominantly by inhibiting I KCa . Moreover, protein kinase C appears to be the main kinase involved in the ceramide inhibition of I KCa .