《Molecular Bases for the Asynchronous Activation of Sodium and Potassium Channels Required》.pdfVIP

Neuron Report Molecular Bases for the Asynchronous Activation of Sodium and Potassium Channels Required for Nerve Impulse Generation ´ ˆ 1 1 1 1,* Jerome J. Lacroix, Fabiana V. Campos, Ludivine Frezza, and Francisco Bezanilla 1Department of Biochemistry and Molecular Biology, University of Chicago, 929 East 57th Chicago, IL 60637, USA *Correspondence: fbezanilla@ /10.1016/j.neuron.2013.05.036 SUMMARY 1952), while pore opening in Kv channels typically requires the rearrangement of four (Smith-Maxwell et al., 1998). While this Most action potentials are produced by the sequen- distinct feature may contribute to a slightly faster pore opening tial activation of voltage-gated sodium (Nav) and in Nav channels, it is known that the main factor underlying potassium (Kv) channels. This is mainly achieved by fast activation of Nav channels is the rapid rearrangement of their the rapid conformational rearrangement of voltage- VS (Armstrong and Bezanilla, 1973; Bezanilla et al., 1982). After sensor (VS) modules in Nav channels, with activation 60 years since the landmark work of Hodgkin and Huxley (Hodg- kinetics up to 6-fold faster than Shaker-type Kv chan- kin and Huxley, 1952), the molecular bases for the kinetic differ- ences between voltage sensors of Na+ and K+ channels remain nels. Here, using mutagenesis and gating current unexplained. measurements, we show that a 3-fold acceleration