MEMBRANE STIFFNESS AND CHANNEL FUNCTION

Alterations in the stiffness of lipid bilayers are likely to constitut e a general mechanism for modulation of membrane protein function. Gra micidin channels can be used as molecular force transducers to measure such changes in bilayer stiffness. As an application, we show that N- type calcium channel inactivation is shifted reversibly toward negativ e potentials by synthetic detergents that decrease bilayer stiffness, Cholesterol, which increases bilayer stiffness, shifts channel inactiv ation toward positive potentials. The voltage activation of the calciu m channels is unaffected by the changes in stiffness, Changes in bilay er stiffness can be predicted from the molecular shapes of membrane-ac tive compounds, which suggests a basis for the pharmacological effects of such compounds.