Abstract.
Sarcolemmal adenosine 5′-triphosphate-sensitive K+ channels (KATP) are dramatically up-regulated by a membrane phospholipid, phosphatidyl-inositol-4,5-bisphosphate (PIP2). During ischaemia, L-palmitoylcarnitine (L-PC), a fatty acid metabolite, accumulates in the sarcolemma and deranges the membrane lipid environment. We therefore investigated whether alteration of the membrane lipid environment by L-PC modulates the KATP channel activity in inside-out patches from guinea-pig ventricular myocytes. L-PC (1 µM) inhibited KATP channel activity, without affecting the single channel conductance, through interaction with Kir6.2. L-PC simultaneously enhanced the ATP sensitivity of the channel [concentration for half-maximal inhibition (IC50) fell from 62.0±2.7 to 30.3±5.5 µM]. In contrast, PIP2 attenuated the ATP sensitivity (IC50 343.6±54.4 µM) and restored Ca2+-induced inactivation of KATP channels (94.1±13.7% of the control current immediately before the Ca2+-induced inactivation). Pretreatment of the patch membrane with 1 µM L-PC, however, reduced the magnitude of the PIP2-induced recovery to 22.7±6.3% of the control (P<0.01 vs. 94.1±13.7% in the absence of L-PC). Conversely, after the PIP2-induced recovery, L-PC's inhibitory action was attenuated, but L-PC partly reversed the PIP2-mediated decrease in the ATP sensitivity (IC50 fell from 310±19.2 to 93.1±9.8 µM). Thus, interaction between L-PC and PIP2 in the plasma membrane appears to regulate KATP channels.
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Received after revision: 23 July 2000
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Haruna, T., Horie, M., Takano, M. et al. Alteration of the membrane lipid environment by L-palmitoylcarnitine modulates KATP channels in guinea-pig ventricular myocytes. Pflügers Arch - Eur J Physiol 441, 200–207 (2000). https://doi.org/10.1007/s004240000428
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DOI: https://doi.org/10.1007/s004240000428