Molecular Properties Molecular Properties of Voltage Gated of Voltage Gated ChannelsChannels

Ion SelectivityIon Selectivity

Charge on MouthCharge on Mouth

Size and charge near Size and charge near center, energy of center, energy of hydrationhydration

The Sodium ChannelThe Sodium Channel

Kandel 7-3Kandel 7-3

Na channels belong to a Na channels belong to a

family of channels family of channels

(ionophores) that are(ionophores) that are

allosteric (shape changing)allosteric (shape changing)

Shape changes are modifiedShape changes are modified

by changes in membraneby changes in membrane

potential (voltage gated)potential (voltage gated)

Or chemicallyOr chemically

Chemical modificationsChemical modifications

are involved in shortare involved in short

term memories (moreterm memories (more

later).later). Kandel 7-11Kandel 7-11

Voltage sensing by NaVoltage sensing by Na

channelschannels is achieved byis achieved by

the the subunit depicted subunit depicted

here. There are fourhere. There are four

subunit domains (MI – IV)subunit domains (MI – IV)

of six of six helices each. helices each.

Together these formTogether these form

the pore. P portions ofthe pore. P portions of

these domains providethese domains provide

a charged lining. a charged lining.

Kandel 10-9 modifiedKandel 10-9 modified

S4 helices are believed to provide the voltage sensing.S4 helices are believed to provide the voltage sensing.The entire channel is a heterotetramer, made of the large The entire channel is a heterotetramer, made of the large glycoprotein glycoprotein subunitsubunit forming the aqueous pore andvoltage sensor, and three smaller polypeptide units, , and (?), and (?), The inactivation gate is located onThe inactivation gate is located on the cytoplasmic side the cytoplasmic side

of the of the subunit (recall pronase experiments). subunit (recall pronase experiments).

Molecular Structure of the Sodium ChannelMolecular Structure of the Sodium Channelthe the Subunit Stretched Out Subunit Stretched Out

Kandel 10-9 modifiedKandel 10-9 modified

Molecular Structure of the Sodium Molecular Structure of the Sodium ChannelChannel

The The Subunit – A View from the Subunit – A View from the TopTop

Kandel 10-10Kandel 10-10

Molecular Structure of the Sodium Molecular Structure of the Sodium ChannelChannel

A Model of Voltage DrivenA Model of Voltage DrivenS4 S4 Helical Rotation Helical Rotation

Kandel 10-11Kandel 10-11

Kandel 10-10Kandel 10-10

Arginine residues Arginine residues pushed up and out pushed up and out convey the appearance convey the appearance of movement of 1 of movement of 1 unit positive charge out unit positive charge out of the membrane orof the membrane or1 unit negative charge 1 unit negative charge into the membraneinto the membrane