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CYTOGENETICS
Lesson
[TRANS] LESSON 04: TRANSPORT ACROSS CELL MEMBRANE & CELL SIGNALING
NA+ PUMP & K+ CHANNELS
● It is how membrane potential is maintained
● The Na pump uses the energy of ATP
hydrolysis to pump Na+ out of animal cells
and K+ in. In this way, the pump helps keep the
cytosolic concentrations of NA+ low and K+ high
● “Na is extracellular cation, and K is intracellular
cation”
NA+ PUMP
● Accounts for 30% of ATP-use ● Pumps Na+ out, carries K+ in ● Also known as Na+-K+ ATPase or the Na+-K+ pump ● 3 Na+ out ● 2 K+ in ● Creates a steep concentration gradient of both ions ● Na+ gradient produces most energy
● “In this case Na is higher concentration outside.
Each time it pumps out 3 Na+ ions and carries in
2 K+ ions, so dili equal ang transport sa ion.
That is why the outside is more positive than the
inside of the cell”
● d
K+ LEAK CHANNELS
● Allow K+ to move freely across the membrane ● Increases cations in the extracellular space ● Decreases cations in the extracellular space ● Created the negative resting membrane potential
● “Diba K+ is inside man, so what it does is it
constantly releases K+ outside of the cell. Now
what does this do? So this increases the cations
in the extracellular space and this creates the
negative resting membrane potential. So this is
you K+ leak channel”
NEURONAL COMMUNICATION
PARTS OF NEURON
● This is how neurons talk to each other ● A typical neuron has a cell body, a single axon, and multiple dendrites. The axon conducts electrical signals away from the cell body toward its target cells, while the multiple dendrites receive signals from the axons of other neurons. The red arrows indicate the direction in which signals travel. ○ Cell body → where nucleus is found ○ Axon → long appendage of neuron that is leading to another neuron on one end is called “nerve terminals” ○ Multiple dendrites → branching to increase surface area of reception
NEURAL CIRCUIT
● Action potential or nerve impulse → long distance electrical signals up to 100m/s ● This is how electrical signals travel from one neuron to another
● “Our neural circuit is connected all throughout
our body, from the brain to your nerves and it
moves very fast”
ACTION POTENTIAL
● The way neural circuit communicate to each other is through action potential ○ Also known as the nerve impulse ● Triggered by depolarization of the cell membrane ● Sudden influx of Na+
VOLTAGE-GATED NA+ CHANNEL
● Triggered by depolarization of the cell membrane ● Causes sudden influx of Na+ ● Automatically shuts off after ~1 millisecond ○ Open-state & Close-state
CONFORMATIONS OF NA+ CHANNEL
● “So here, resting pa siya (closed). So when it
reaches a certain threshold here, (open) na siya,
there’s a sudden influx of Na+ cations, so
mutaas ang voltage. And at this point it closes
itself automatically and resets. It is
voltage-regulated.”
SPREAD OF ACTION POTENTIAL
● An action potential propagates along the length of an axon. The changes in the Na+ channels and the consequent flow of Na+ across the membrane (red arrows) alters the membrane potential and gives rise to the traveling action potential
SYNAPSES
● Presynaptic cell → transmitting ● Postsynaptic cell → receiving ● Synaptic cleft → gap between cells
CONTACT-DEPENDENT SIGNALING
● Direct physical contact through signal molecules lodged in the plasma membrane of the signaling cell and receptor proteins
RECEPTORS
● Activated by specific signal molecules
CELL SURFACE RECEPTORS
● Most extracellular signal molecules are large and hydrophilic and are therefore unable to cross the plasma membrane directly; instead, they bind to cell-surface receptors, which in turn generate one or more intracellular signaling molecules in the target cell.
INTRACELLULAR RECEPTORS
● Some small, hydrophobic, extracellular signal molecules pass through the target cell’s plasma membrane and bind to intracellular receptors—in the cytosol or in the nucleus (as shown here)—that then regulate gene transcription or other functions.
TARGET CELL RESPONSE
● Signals can cause different responses depending on the target cell type. ● Effector proteins ○ Have a direct effect on the behavior of the target cell ● Responses also depend on the combinations of signals received ● The speed of the response depends on availability of effector proteins
CELL SURFACE RECEPTORS
● Recognizes the extracellular signal and generates new intracellular signals in response
INTRACELLULAR SIGNALING PATHWAYS
● Functions: ○ Relay signals ○ Amplify signals ○ Integrate/combine signals ○ Distribute to effector proteins ○ Provide feedback
TYPES OF FEEDBACK LOOPS
POSITIVE FEEDBACK
● Enhances response
NEGATIVE FEEDBACK
● Diminishes response
MOLECULAR SWITCHES
● Most common functions of intracellular signaling molecules ● Possible actions: ○ Stimulate ○ Suppress ● Each activation step has an inactivation mechanism
TYPES OF MOLECULAR SWITCHES
ACTIVATED OR INACTIVATED BY
PHOSPHORYLATION
● This is most common ● Protein kinase ○ Attaches phosphate group ● Protein phosphatase ○ Takes the phosphate off again ● Phosphorylation cascades ○ Activated protein is also protein kinases ● Types of protein kinases ○ Serine/threonine kinases ■ Most common ○ Tyrosine kinases
GTP-BINDING PROTEINS
● Active State ○ GTP attached ● Inactive state ○ GDP attached ● Have intrinsic GTP-hydrolyzing (GTPase) activity ○ Auto-shut off by hydrolyzing their bound GTP to GDP
TYPES OF BINDING PROTEINS
G-PROTEIN TARGETS
● Ions channels ● Membrane-bound enzymes ● Because each activated enzyme generates many molecules of these second messengers, the signal is greatly amplified at this step in the pathway. ● The signal is relayed onward by the second messenger molecules, which bind to specific signaling proteins in the cell and influence their activity TAKEAWAYS
● The lipid bilayer of cell membranes is highly
permeable to small, non- polar molecules such
as oxygen and carbon dioxide and, to a lesser
extent, to very small, polar molecules such as
water. It is highly impermeable to most large,
water-soluble molecules and to all ions.
● Transfer of nutrients, metabolites, and inorganic
ions across cell membranes depends on
membrane transport proteins.
● Cell membranes contain a variety of transport
proteins that function either as transporters or
channels, each responsible for the transfer of a
particular type of solute.
● Channel proteins form pores across the lipid
bilayer through which solutes can passively
diffuse.
● Both transporters and channels can mediate
passive transport, in which an uncharged solute
moves spontaneously down its concen- tration
gradient.
● For the passive transport of a charged solute, its
electrochemical gradient determines its direction
of movement, rather than its con- centration
gradient alone.
● Transporters can act as pumps to mediate active
transport, in which solutes are moved uphill
against their concentration or electrochemi- cal
gradients; this process requires energy that is
provided by ATP hydrolysis, a downhill flow of
Na+ or H+ ions, or sunlight.
● Transporters transfer specific solutes across a
membrane by under- going conformational
changes that expose the solute-binding site first
on one side of the membrane and then on the
other.
● The Na+ pump in the plasma membrane of
animal cells is an ATPase; it actively transports
Na+ out of the cell and K+ in, maintaining a
steep Na+ gradient across the plasma
membrane that is used to drive other active
transport processes and to convey electrical
signals.
● Ion channels allow inorganic ions of appropriate
size and charge to cross the membrane. Most
are gated and open transiently in response to a
specific stimulus.
● Even when activated by a specific stimulus, ion
channels do not remain continuously open: they
flicker randomly between open and closed
conformations. An activating stimulus increases
the propor- tion of time that the channel spends
in the open state.
● The membrane potential is determined by the
unequal distribution of charged ions on the two
sides of a cell membrane; it is altered when
these ions flow through open ion channels in the
membrane.
● In most animal cells, the negative value of the
resting membrane potential across the plasma
membrane depends mainly on the K+ gradient
and the operation of K+-selective leak channels;
at this rest- ing potential, the driving force for the
movement of K+ across the membrane is almost
zero.
● Neurons produce electrical impulses in the form
of action potentials, which can travel long
distances along an axon without weaken- ing.
Action potentials are propagated by
voltage-gated Na+ and K+ channels that open
sequentially in response to depolarization of the
plasma membrane.
● Voltage-gated Ca2+ channels in a nerve
terminal couple the arrival of an action potential
to neurotransmitter release at a synapse.
Transmitter-gated ion channels convert this
chemical signal back into an electrical one in the
postsynaptic target cell.
● Excitatory neurotransmitters open
transmitter-gated cation channels that allow the
influx of Na+, which depolarizes the postsynaptic
cell’s plasma membrane and encourages the
cell to fire an action potential. Inhibitory
neurotransmitters open transmitter-gated Cl–
channels in the postsynaptic cell’s plasma
membrane, making it harder for the membrane
to depolarize and fire an action potential.
● Complex sets of nerve cells in the human brain
exploit all of the above mechanisms to make
human behaviors possible.
