Voltage-Gated Ion Channels

• Voltage-dependent ion channels play a fundamental role in the generation and propagation
of the nerve impulse and in cell homeostasis.

• The voltage sensor is a region of the protein bearing charged amino acids that relocate upon changes in
the membrane electric field.

Segments (S5 and S6) and the pore loop

were found to be responsible for ion conduction.

Lipid bilayer
Transmembrane
segment (cylinder)

Voltage sensor Pore

part of the channel

General architecture of voltage-gated channels (Na+ and Ca2+).The “+” or “-“ signs
indicate charges that have been implicated in voltage sensing.
Voltage-Gated Ion Channels
The Gate The ion conduction through the pore may be interrupted by closing a gate

Lipid bilayer

Closed states

voltage gated ion channel

field-effect transistor

Open states

voltage gated ion channel

field-effect transistor

Comparison between a field-effect transistor (FET) and a voltage gated ion channel. The FET transistor is
represented as a p-channel device to make a closer analogy to a cation selective voltage-gated channel. In the
FET, D is the drain, S is the source, and G is the gate.
Voltage-Gated Ion Channels
Ionic and gating currents in Shaker-IR K+ channel

Time course of ionic currents for pulses to

the indicated potentials starting and
returning to –- 90 mV The voltage dependence of the open probability
and the charge moved per channel.

Time course of the gating currents for the

pulses indicated.
Voltage-Gated Ion Channels
Typical gating current trace

Gating current recorded

at 10-kHz bandwidth.

When the bandwidth is increased to

200 kHz, the first surge of current is the
predominant amplitude

The time course of the charging of the

membrane capacitance for the
experiment in (b).
Voltage-Gated Ion Channels
Current fluctuations in gating currents

Top trace is the time course of a pulse to Top trace is the time course of a smaller pulse to
+10 mV; middle trace is the variance and - 40 mV; middle trace is the variance; lower trace
bottom trace is the mean computed from is the mean computed from hundreds of traces.
several hundred traces.
Voltage-Gated Ion Channels
Three models of the voltage sensor

Helical screw model Transporter model. Paddle model.

Positively charged residues