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Article
Regulation of Calcium Channel Activity by Lipid Domain Formation in Planar Lipid Bilayers
Biophysical Journal (2003)
  • Brian Cannon
  • Martin Hermansson
  • Sandor Györke
  • Pentti Somerharju
  • Jorma A Virtanen
  • Kwan H Cheng, Trinity University
Abstract

The sarcoplasmic reticulum channel (ryanodine receptor) from cardiac myocytes was reconstituted into planar lipid bilayers consisting of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) in varying ratios. The channel activity parameters, i.e., open probability and average open time and its resolved short and long components, were determined as a function of POPE mole fraction (XPE) at 22.4°C. Interestingly, all of these parameters exhibited a narrow and pronounced peak at XPE ≈ 0.80. Differential scanning calorimetric measurements on POPE/POPC liposomes with increasing XPE indicated that the lipid bilayer enters a composition-driven transition from the liquid-crystalline state to the gel state at 22.4°C when XPE approaches 0.80. Thus, the peaking of the reconstituted channel activity at XPE ≈ 0.80 in the planar bilayer could result from the appearance of gel/liquid-crystalline domain boundaries at this POPE content. Lipid packing at domain boundaries is known to be looser as compared to the homogenous gel or liquid-crystalline state. We propose that the attractive potential of packing defects at lipid domain boundaries and entropic excluded-volume effects could result in the direct interactions of the transmembrane region of the channel protein with the lipid-packing defects at the lipid/protein interface, which could thus provide a favorable environment for the open state of the protein. The present findings indicate that the activity of the sarcoplasmic reticulum calcium channel could be modulated by lipid domain formation upon slight changes in membrane lipid composition in vivo.

Keywords
  • calcium channel,
  • calcium ion,
  • lipid,
  • liposome,
  • ryanodine receptor,
  • unclassified drug,
  • animal cell,
  • liquid crystal,
  • phase transition,
  • protein function,
  • rat,
  • lipid bilayers,
  • membrane fluidity
Publication Date
August, 2003
Citation Information
Cannon, B., Hermansson, M., Györke, S., Somerharju, P., Virtanen, J. A., & Cheng, K. H. (2003). Regulation of calcium channel activity by lipid domain formation in planar lipid bilayers. Biophysical Journal, 85, 933-942. doi: 10.1016/S0006-3495(03)74532-9