Ion Channels

	John Koester
	jdk3

Outline

	Why ion channels?
	Channel structure
	Ion channels have three basic functional properties
		Conduct
		Select
		Gate
	Evolutionary relationships between ion channels
	Various factors contribute to ion channel diversity

Ions Cannot Diffuse Across the Hydrophobic Barrier of the Lipid Bilayer

Ion Channels Provide a Polar Environment for Diffusion of Ions Across the Membrane

Specialized Functions of Ion Channels

	Mediate the generation, conduction and transmission of electrical signals in the nervous system
	Control the release of neurotransmitters and hormones
	Initiate muscle contraction
	Transfer small molecules between cells (gap junctions)
	Mediate fluid transport in secretory cells
	Control motility of growing and migrating cells
	Provide selective permeability properties important for various intracellular organelles

Outline

	Why ion channels?
	Channel structure
	Ion channels have three basic functional properties
		Conduct
		Select
		Gate
	Evolutionary relationships between ion channels
	Various factors contribute to ion channel diversity

Channels are Made Up of Subunits

Outline

	Why ion channels?
	Channel structure
	Ion channels have three basic functional properties
		Conduct
		Select
		Gate
	Evolutionary relationships between ion channels
	Various factors contribute to ion channel diversity

•Ion Channels Act As Catalysts

Unlike Channels, Ion Pumps Do Not Provide a Continuous Pathway Through the Membrane

Outline

	Why ion channels?
	Channel structure
	Ion channels have three basic functional properties
		Conduct
		Select
		Gate
	Evolutionary relationships between ion channels
	Various factors contribute to ion channel diversity

Ion Channels are Selectively Permeable

Structure of K⁺ Channel Has
Multiple Functional Adaptations

Outline

	Why ion channels?
	Channel structure
	Ion channels have three basic functional properties
		Conduct
		Select
		Gate
	Evolutionary relationships between ion channels
	Various factors contribute to ion channel diversity

Single Channel Openings are All-or-None in Amplitude,
With Stochastically Distributed Open and Closed Times

There are Two Major Types of Gating Actions

Gating Can Involve Conformational Changes Along the Channel Walls

Gating Can Involve Plugging the Channel

Gating Can Result from Plugging by Cytoplasmic or Extracellular Gating Particles

There are Five Types of
Gating Controls

1) Ligand Binding

2) Phosphorylation

Slide 23

Slide 24

Modifiers of Channel Gating

Binding of Exogenous Ligands Can Block Gating

Ion Permeation Can be Prevented by
Pore Blockers

Exogenous Modulators Can Modify the Action of Endogenous Regulators

Outline

	Why ion channels?
	Ion channels have three basic functional properties
		Conduct
		Select
		Gate
	Evolutionary relationships between ion channels
	Various factors contribute to ion channel diversity

Evolution Operates More Like a Tinkerer
Than an Engineer

Ion Channel Gene Superfamilies

Ion Channel Gene Superfamilies

Ion Channel Gene Superfamilies

Outline

	Why ion channels?
	Channel structure
	Ion channels have three basic functional properties
		Conduct
		Select
		Gate
	Evolutionary relationships between ion channels
	Various factors contribute to ion channel diversity

Different Genes Encode Different
Pore-Forming Subunits

Different Pore-Forming Subunits
Combine in Various Combinations

The Same Pore-Forming Subunits Can
Combine with Different Accessory Subunits

Alternative Splicing of Pre-mRNA

Post-Transcriptional Editing of pre-mRNA

Generator Potentials, Synaptic Potentials and Action Potentials All Can Be Described by the Equivalent Circuit Model of the Membrane

Equivalent Circuit Model of the Neuron

The Lipid Bilayer Acts Like a Capacitor

Change in Charge Separation Across
Membrane Capacitance is Required to Change Membrane Potential

The Bulk Solution Remains Electroneutral

Each K⁺ Channel Acts as a Conductor (Resistance)

Ion Channel Selectivity and Ionic Concentration Gradient Result in an Electromotive Force

An Ion Channel Acts Both as a
 Conductor and as a Battery

An Ionic Battery Contributes to V_M in Proportion to the
Membrane Conductance for that Ion

Experimental Set-up for
Injecting Current into a Neuron

Because of Membrane Capacitance,
Voltage Always Lags Current Flow

Length Constant l = √r_m/r_a