Probing Membrane Bilayer Interactions of 1,4-Dihydropyridine Calcium Channel Blockers

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Abstract
The results of this study demonstrate that the equilibrium nonspecific binding of DHP Ca2+ channel blockers to the membrane bilayer is highly dependent on cholesterol content. The molecular explanation for this observation appears to be related to the fact that cholesterol and DHPs occupy a similar molecular location in the membrane hydrocarbon core (Fig. 4). The membrane location of amlodipine may also be critical for subsequent receptor recognition and binding to voltage-sensitive Ca2+ channels in peripheral and CNS tissue. Finally, changes in the cholesterol content of neural plasma membranes isolated from diseased cortical regions of subjects with AD were reported and may be indicative of a general defect in lipid metabolism. Further studies are underway to characterize in greater detail possible changes in cholesterol content with aging and AD. The implication of these changes for structure/function relationships in the membrane is also being explored.

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