Start Over

Inactivation of potassium channels by ceramide in rat pancreatic β-cells.

Authors :: Quiroz-Acosta T
Bermeo K
Arenas I
Garcia DE
Source :: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2023 Feb; Vol. 735, pp. 109520. Date of Electronic Publication: 2023 Jan 13.
Publication Year :: 2023
Abstract: Lipid regulation of ion channels is a fundamental mechanism in physiological processes as of neurotransmitter release and hormone secretion. Ceramide is a bioactive lipid proposed as a regulator of several voltage-gated ion channels including potassium channels (Kv). It is generated either de novo or by sphingomyelin (SM) hydrolysis in membranes of mammalian cells. In pancreatic β-cells, ceramide is the main sphingolipid associated with lipotoxicity and likely involved in cell dysfunction. Despite of the wealth of information regarding regulation of potassium channels by ceramides, the regulation of Kv channels by accumulated ceramide in native pancreatic β-cells has not been investigated. To do so, we used either the C2-ceramide, a cell-permeable short-chain analogue, or a sphingomyelinase (SMase C), a hydrolase causing ceramide to elevate from an endogenous production, in pancreatic β-cells of rat. C2-ceramide markedly accelerates steady-state current inactivation according to kinetic changes in the channel machinery. Interestingly, only C2-ceramide accelerates current inactivation while SMase C decreases both, peak-current and step-current amplitude supporting differential effects of ceramide derivatives. A specific inhibitor of the Kv2.1 channel (GxTX-1E), readily inhibits a fraction of the Kv channel current while no further inhibition by C2-ceramide superfusion can be observed supporting Kv2.1 channel involvement in the ceramide inhibition. Thus, intramembrane ceramide accumulation, as a lipidic metabolite released under cell-stress conditions, may alter pancreatic β-cell repolarization and secretion. These results may provide a new insight regarding lipid-protein regulation and advance our understanding in ceramide actions on Kv channels in pancreatic β-cells.<br />Competing Interests: Declaration of competing interest No conflict of interest, financial, and otherwise are declared by authors.<br /> (Copyright © 2023 Elsevier Inc. All rights reserved.)