Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

Chapter IV Book Notes: Channels and Transporters

9/29/16 3:50 P

Active transporters are membrane proteins that establish and maintain ion
gradients
Ion channels are Transmembrane proteins that contain a pore to allow
particular ions to cross the neuronal membrane
Voltage gated channels open and close in response to magnitude of the
electrical potential
Other types of channels are gated by extracellular signals like
neurotransmitters or 2nd messengers
Ion Channels Underlying Action Potentials
H&H could only resolve the aggregate current resulting from the flow of ions
through many channels, not through single channels
Microscopic currents à currents that flow through single channels
Macroscopic currents à currents flowing through many channels over a
region of space
Microscopic and macroscopic currents match up for Na+
• 1) currents direction matches
• 2) same time course opening and closing
• voltage dependence
Summary: patch clamping has allowed direct observation of microscopic
ionic current flowing through single ion channels are responsible for the
macroscopic conductance’s and currents that underlie the AP
Ionic selectivity = ion channels are able to discriminate between various
ions
Voltage gated = opening is influenced by membrane potentials
Voltage sensor = detects the potential across a membrane
Inactivation differences between K+ and Na+ channels
Diversity of Ion Channels
Some channels respond to membrane potentials while other respond to
chemical signals intra or extracellularly

Ion channel genes contain a large number of coding regions that can be
spliced together in different ways so a single gene can give rise to channel
proteins with different functions
Voltage gated Ion Channels
Major voltage gated ion channels are ones that are selectively permeable to
ions Na+ K+ Cl- and Ca2+
Many different genes have been discovered for each type of VGC
• Example: 10 different kinds of Na+ channels
Ca2+ channels are significant
• Some give rise to AP’s just like Na+ does
• Some control the shape of the AP generated primarily by Na+
conductance changes
• Many processes regulated by these channels
• Most IMPORTANT job of Ca2+ channels is the release of
neurotransmitters at the synapse of a cell
• 16 different Ca2+ channels
• have different activation and inactivation methods
K+ channels
• largest and most diverse of VGC’s
• some take a while to activate (squid axon) and some do not
• most IMPORTANT job is regulating RMP
Cl- Channels
• Control excitability
• Contribute to RMP
• Regulate cell volume
Ligand Gated Ion Channels
•
•
•

Most important ones are those activated by neurotransmitters
Essential for synaptic transmission
LGC are usually less selective, allowing more than one ion to travel
through pores

•

•

Some LCG are distinguished by ligand binding sites of the
intracellular surface and are sensitive to ions on the inside of the
cell
o These act with 2nd messengers like Ca2+, cAMP or cGMP
o Example: Ca2+ activated K+ channels
§ Main function: convert intracellular chemical signals into
electrical information
§ Important for sensory transduction à turning odor into
an electrical signal
Some LCG are found in the membranes of some organelles like the
ER

Stretch and Heat-Activated Channels
Channels that respond to heat or membrane deformation
Heat activated channels are specialized to detect specific temperature
ranges sometimes even cold ones, and can send signals that are sensations
of pain and temperature to mediate inflammation
Other ion channels respond to distortion of plasma membrane à some
enable hearing by allowing auditory hair cells to respond to sound waves
The Molecular Structure of Ion Channels
Studies using mutagenesis to explore the expression of ion channels in
Xenopus oocytes have helped scientists learn a lot about channels
Studies reveal a general transmembrane architecture common to all the
major ion channel families
• Na+ channels are repeating motifs of 6 membrane spanning regions
that are repeated 4 times to make 24 transmembrane regions
o B subunits can regulate this function
• K+ channels span the membrane 6 times, but some like one
bacterial channel only span twice
• Two membrane spanning domains form a central pore through
which ions can diffuse, one of these domains contains a protein loop
that confers ion selectivity which allows only certain ions to diffuse
through

•

The voltage sensor in VGC is a transmembrane helix containing a
number of positively charged amino acids causing the helix to
change position

Direct information about structure has come from X-Ray crystallography
studies of K+ channels
• Studies of bacterial K+ channels
• These studies showed that the channel is formed by subunits that
each cross the plasma membrane twice à between these two
membrane spanning structures is a loop that inserts into the
plasma membrane à four of these units extended to form a
•
•

•

channel
Selectivity filter is what makes it specific to K+ and not other
cations
presence of multiple K+ ions within the selectivity filter causes
electrostatic repulsion between these ions that helps speed up their
transit through the filter à permits rapid ion flux
Voltage sensors on VGC have positively charged amino acids that
respond to changes in membrane potential (which move in
response to depolarization) à force is exerted on the helical
structure and pulls pore open or closed

Active Transporters Create and Maintain Ion Gradients
Nerve cells maintain ion concentration gradient across their surface
membranes!! Even though none of the physiological ions (Na+ K+ Ca2+,
and Cl- are in electrochemical equilibrium
The work of generating and maintaining ionic concentration gradients for
particular ions is carried out by active transporters
Active transporters do this by forming complexes with the ions they are
translocating
• This is much slower than other forms of ion movement because of
the binding and unbinding
• Active transporters gradually store energy in the form of ion
concentration gradients, whereas the opening of ion channels
rapidly dissipates this stored energy during signaling events

Active transporters all move ions against electrochemical gradient
• This requires energy consumption in one of two ways
o ATPase pumps that get their energy directly from
hydrolyzing ATP
§ Ex: the Na+/K+ pump which maintains transmembrane
concentrations for both ions
§ Also, Ca2+ pumps work by removing calcium from cells
§
o Ion exchangers are transporters that do not use ATP but
depend on the electrochemical gradients of other ions as an
energy source
§ This type takes one or more ions UP while taking one
(usually Na+) DOWN
§ Example: Na+/Ca2+ which also helps to keep calcium
levels inside the cell low
§ Na+/H+ exchanger helps set pH
§ There is an Na+/K+/Cl- co transporter
Functional Properties of the Na+/K+ pump
Best understood, uses 20-40% of the brains energy consumption (indicating
its importance)
Studies showed that removing intracellular Na+ requires cellular metabolism
2 K+ pumped in while 3 Na+ pumped out
• Since this pump creates current that can hyperpolarize cell it is said
to be electrogenic
• Smaller current because slower than channels
• Even though its small, it influences membrane potential greatly
o Example: prolonged stimulus of unmyelinated axons produce
substantial hyperpolarization à Na+ enters through VGC
during this stimulation and accumulates

---