Lecture 13 Flashcards
H and H’s pivotal studies provided avenues for understanding other aspects of an action potential
For example, how much voltage is required for an action potential to occur, i.e., what is the action potential voltage threshold?
How does location of the synapse play a role in AP’s being initiated?
A NT is released by the synapse to evoke an EPSP, by the time the EPSP reaches the axon, it is below threshold so it does not release an AP. This time when the synapse is closer and it releases a NT, the EPSP that reaches the axon is above threshold and so is is able to fire an AP.
What is an AIS?
AIS is the region of the axon where AP’s initiate. It stand for axon initial segment. The AIS can be variable in its location, even in the same neuron where location is modulated by neurohormones.
AP in a nutshell (part 1)
At the axon Nav and Kv channels are at bay waiting for depolarization. Voltage threshold is the tipping point at which enough axonal Na channels are activated so that they can overcome outward K leak currents, as well as any other Kv channel through which currents can move out from.
AP in a nutshell (part 2)
Once over the tipping point, the Nav currents activate even more Nav channels, creating an all or none response. This causes the rising phase of the action potential.
AP in a nutshell (part 3), Kv are like sleeping giants
Kv channels are not quick to respond to depolarization caused by EPSP’s or Nav channels. Once they are activated, they conduct massive outward K currents that repolarize the membrane, causing the falling phase of the action potential. Activated Kv channels temporarily drive the Vm below the RMP, generating the AP undershoot, aka the afterhyperpolarization.
Important note on AP’s
The AP threshold is not static. It can change depending on the RMP and the expression levels and gating properties of Nav, Kv, and other channels expressed in the axonal membrane and the AIS.
How to understand how threshold voltage works?
To understand this we need to understand the different properties of Nav and Kv channels. Plotting the peak conductances of Nav and Kv channels at different depolarizing voltages generates the corresponding conductance curves.
What gives rise to Na+ or K+ conductances in a squid axon or neuron?
Populations of Nav or Kv channels present in the membrane. These conductance curves the activation of entire populations of Nav and Kv channels
Why do the peak Na+ and K+ conductances begin saturating at voltage steps greater than +20mV?
The membrane has a finite number of Na and K channels, we max out the number of channels that can be activated at 20mV or more.
What depolarizing voltage step is required such that we activate/open ~50% of the Nav and Kv channel populations?
-10 mV
Interpreting the curves (slide 16 graph)
Depolarizing the membrane voltage to -60 mV will not have any affect on the conductances of Na+ or K+. So a voltage step from a negative voltage, say -70 mV, to -60 mV will not open (activate) any Nav or Kv channels.
Interpreting the curves (slide 17 graph)
Instead, depolarizing Vm to above 40 mV does change the membrane conductance to Na+ and K+ because that is the point at which Nav and Kv channels are activated. Conductance curves can be interpreted as the percentage of channels that open when the Vm is depolarized to various voltages.
This makes sense when you think about the Nav and Kv voltage sensors because at higher depolarizations, the s4 helices is able to slide out of the membrane easily.
To fire or not to fire
Recall that H and H used the voltage clamp to observe how holding voltage (akin to RMP) affects the inactivation of Nav channels. Note that only Nav channels in the squid showed inactivation.
How did H and H characterize the Nav channel steady state properties?
By holding Vm through a series of voltages (RMP’s) and then stepping to a fixed depolarized voltage to open Nav channels.
