Topic 12: Neuronal Signaling Flashcards
What is a neuron?
class of excitable cells, communicate via an electrical impulse
one of the typical cells that are studied when looking at cell signaling is the neuron
capacity to integrate and sense tens of thousands of different inputs
flow of impulse is unidirectional
What is the path of signals through the neuron?
dendrite –> cell body –> axon hillock –> axon –> synapse
What is resting potential?
generated by the sodium potassium pump
at the resting state, some leakage of particularly potassium occurs through potassium channels
3 Na+ out, 2 K+ in
What is depolarization?
communication in the neuron is due to brief local changes in voltage
local change in membrane permeability due to opening and closing of voltage gated ion channels = opening of Na+ channels
Na+ rushes into cell –> depolarization
voltage gated channels have similar structure
voltage changes greater than -50 mV causes channel opening, sodium channels are specific and open faster then K+ channels
threshold voltage –> minimum levels of depolarization required for channel opening, voltage required to shift channels open
then slower voltage gated K+ channels open, slow to open and slow to close leading to eventual hyperpolarization, potassium channels are specific
What is the structure of potassium channels?
tetrameric proteins composed of four identical subunits each with 6 alpha helical TMD
S4 alpha helix is likely the voltage sensor
4 subunit associates into tetrameric K+ channel
selectivity filter of K+ can form stable associations with K+ but not Na+ (different sizes)
S4 can shift position in response to changing membrane voltage, contains basic positive amino acids (attracted to side of membrane of opposite charge)
selectivity filter: negative amino acids sit into the channel, ionic bonds that form will strip ion of hydration shell, ion is attracted to an amino acid of opposite charge
What is the process of opening and closing the potassium channels?
the channel is closed when the voltage inside the cell is about -70 mV
voltage change across membrane reaches threshold, cause S4 domain to shift, opens channel, BUT opening is relatively slow
inactivating particle plugs channel, creates absolute refractory period, channel temporarily cannot be opened
What is the structure of sodium channels?
monomeric (single) protein with 4x6 membrane spanning segments
each domain contains 6 membrane spanning alpha-helices
contains inactivating partide
has selectivity filter specific to Na+, size smaller than K+, amino acids in filter associate with Na+ better than K+
Na+ channels are fast to open
How does depolarization spread down the neuron?
depolarization spreads down the neuron because of the diffusion of ions to adjacent segments of the axon away from initial site of depolarization
passive spread of depolarization causes opening of additional Na+ channels
action potential is propagated unidirectionally because in absolute refractory period channels are inactivated and in relative refractory period membrane is hyperpolarized
Na+ diffuse within axon which allows threshold to reach in neighboring membrane
AP moves unidirectionally because its easier to achieve threshold moving down axon because of hyperpolarization
What is repolarization?
net efflux of cations (K+ efflux)
K+ channels are slow to open
inactivate ~1 ms after opening
caused by inactivation of K+ channel, absolute refractory period
What is hyperpolarization?
axon is more negative than resting
because K+ channels are slow to close, too much K+ leaves making inside hyperpolarized
What is the synapse?
gap between neuron and next cell
What are electrical synapses?
gap junctions used for rapid communication of electrical impulses over short distances
very important in heart muscle to give a uniform contraction of the ventricles
direct sharing of ions across gap junctions
What are chemical synapses?
action potential stimulates the release of a neurotransmitter (NT)
NT are synthesized at cell body and packaged into vesicles that are trafficked to presynaptic terminus (regulated exocytosis)
How do chemical synapses work?
AP stimulates opening of voltage gated Ca++ channel
Ca++ triggers fusion of vesicles with membrane
receptor binds to NT to elicit a cellular response
elicit a cell response, can be inhibiting or activating
What is the clearance or reuptake of neurotransmitters?
upon NT reuptake the NTs are rapidly reinserted into vesicles by H+/ATP co-transport
neurotransmitters are pretty stable molecules therefore they can persist in synapse, so they must be removed from the synapse
NT can either be degraded in synapse (e.g. ACh is degraded by acetylcholinesterase), or a reuptake inhibitor can be present (cocaine prevents NT reuptake)
