Molecular Properties of Voltage Gated Channels Ion Selectivity Charge on Mouth Size and charge near center, energy of hydration The Sodium Channel Kandel 7-3

Na channels belong to a family of channels (ionophores) that are allosteric (shape changing) Shape changes are modified by changes in membrane potential (voltage gated) Or chemically Chemical modifications are involved in short term memories (more later). Kandel 7-11

Voltage sensing by Na channels is achieved by the  subunit depicted here. There are four subunit domains (MI – IV) of six  helices each. Together these form the pore. P portions of these domains provide a charged lining. Kandel 10-9 modified S4 helices are believed to provide the voltage sensing. The entire channel is a heterotetramer, made of the large glycoprotein  subunit glycoprotein  subunit forming the aqueous pore and voltage sensor, and three smaller polypeptide units  ,   and (?), The inactivation gate is located on the cytoplasmic side of the  subunit (recall pronase experiments). Molecular Structure of the Sodium Channel the  Subunit Stretched Out

Kandel 10-9 modified Molecular Structure of the Sodium Channel The  Subunit – A View from the Top Kandel 10-10

Molecular Structure of the Sodium Channel A Model of Voltage Driven S4  Helical Rotation Kandel Kandel Arginine residues pushed up and out convey the appearance of movement of 1 unit positive charge out of the membrane or 1 unit negative charge into the membrane