Diffusional dynamics of an active rhodamine-labeled 1,4-dihydropyridine in sarcolemmal lipid multibilayers.
A "membrane bilayer pathway" model, involving ligand partition into the bilayer, lateral diffusion, and receptor binding has been invoked to describe the 1,4-dihydropyridine (DHP) calcium channel antagonist receptor binding mechanism. In an earlier study (Chester et al. 1987. Biophys. J. 52:1021-1030), the diffusional component of this model was examined using an active fluorescence labeled DHP calcium channel antagonist, nisoldipine-lissamine rhodamine B (Ns-R), in purified cardiac sarcolemmal (CSL) lipid multibilayers. Diffusion coefficient measurements on membrane-bound drug and phospholipid at maximum bilayer hydration yielded similar values (3.8 x 10(-8) cm2/s). However, decreases in bilayer hydration resulted in dramatically reduced diffusion coefficient values for both probes with substantially greater impact on Ns-R diffusion. These data suggested that hydration dependent diffusional differences could be a function of relative probe location along the bilayer normal. In this communication, we have addressed the relative effect of the rhodamine substituent on Ns-R diffusion complex by examining the diffusional dynamics of free rhodamine B under the same conditions used to evaluate Ns-R complex and phospholipid diffusion. X-ray diffraction studies were performed to determine the Ns-R location in the membrane and model the CSL lipid bilayer profile structure to give a rationale for the differences in probe diffusional dynamics as a function of interbilayer water space.
Mason
R P
RP
Department of Radiology, University of Connecticut Health Center, Farmington 06032.
Chester
D W
DW
D000818:Animals; D002784:Cholesterol; D004058:Diffusion; D004285:Dogs; D005456:Fluorescent Dyes; D006321:Heart / Q000502:physiology; D007700:Kinetics; D008051:Lipid Bilayers; D008961:Models, Structural; D009130:Muscle, Smooth / Q000502:physiology*; D015737:Nisoldipine; D012235:Rhodamines; D012508:Sarcolemma / Q000502:physiology*; D013050:Spectrometry, Fluorescence; D014961:X-Ray Diffraction; D014966:Xanthenes
D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D012235:Rhodamines; D014966:Xanthenes; C022027:lissamine rhodamine B; D015737:Nisoldipine; D002784:Cholesterol