The voltage sensor in voltage-dependent ion channels

The Voltage Sensor in Voltage-Dependent Ion Channels. Physiol. Rev. 80: 555 -592, 2000. -In voltage-dependent Na, K, or Ca channels, the probability of opening is modified by the membrane potential. This is achieved through a voltage sensor that detects the voltage and transfers its energy to the por e to control its gate. We present here the theoretical basis of the energy coupling between:the electric field and the voltage, which allows the inter pretation of the gating, charge that moves in one channel. Movement of the gating charge constitutes the gating current. The properties are described, along with macroscopic data:and gating current noise analysis, in relation to the operation of the voltage sensor and the opening of the channel; Str uctural details of the voltage sensor operation were resolved initially by locating the residues that make up the:voltage sensor using mutagenesis exp eriments and determining the number of charges per channel. The changes in conformation are then analyzed based on the differential exposure of cystei ne or histidine-substituted residues. Site-directed fluorescence labeling i s then analyzed as: another powerful indicator of conformational changes:th at allows time and voltage correlation of local changes seen by the fluorop hores with the global change seen by;the electrophysiology of gating curren ts and ionic currents. Finally, we describe the novel results on lanthanide -based resonance energy transfer that show small distance:changes between r esidues in the channel molecule.:AU of the electrophysiological and the str uctural information are finally summarized in a physical model of a voltage -dependent channel in which a change in membrane potential causes rotation of the S4 segment that changes the exposure of the basic residues from an i nternally connected aqueous crevice at hyperpolarized potentials to, an ext ernally connected aqueous crevice at depolarized potentials.