Dr. Sharif lecture 5
Saturday, December 01, 2012
- Relevance o phasic firing...tday will discuss mechanism
- Shift toward hyopertonic env...VP release to bring back to set point
- 3 regulatory mechanisms that increase firing rate from lect 1:taurine release from astrocytes etc...
- If VP neurons were to increases there firing rate and fire continuously: this leads to a fatigue of the release
○ You get a decrease in the amount of VP released very quickly even though the firing is maintained…
- No VP=no antidioreses
- Cells transition from irr firing to phasic firing to avoid secretory fatigue
- As osmolarity around the cell increases, transition from irr to phasic, the mean firing rae increases and the
frequency within the burst increases and the duration of the burst also increases
- Was not know if the same neuron was doing all these pattern transitions, found out yes…
- 2 neurons firing at the same frequ but diff pattern: one has clusters phasic firing other has a transient irr
firng..the one with phasic firing releases a larger amount of VP in the blood stream...moreca entering the
terminal thus more vesicles fuse…
- Mechanism responsible for secretoryfatigue:
- Accumulation of K outside the neuron...bc of the outward movement of k during the repolarizing phase of the
AP, and if u increase the frequ, the more the K outside
Initially this would change the concentration gradient of K-less driving force for them to exit the cell...more + ions
inside the cell means more depolarization (this means increase in hormone release also)..but then the amount of
VP released starts decreasing...WHY?
- Initially though: if u depolarize the axonal memb. Enough level u get inactivationof V-gated Na
channels...prevent the AP transmission
- Other possibility, the nerve terminals cannot depolarize enough to get Ca influx..
- Stimulated the neural stalk and recorded current in the nerve terminal
- Saw that applying trains of stimuli on stalk to get AP to generate, they could record AP in the nerve terminal.
- But if they increased the stimulation frequency, they saw spike broadening and decrease in spike amp…
1st they saw a memb depolarization which is that axonal spike, then u get the spike that occurs in the nerve
○ Depolarization in the axon doesn’t change in from the 1 to the last
○ But the nerve terminal depolarization, the amp to the spike decreases until u start getting failures
○ As you increase the firing rate, u get more failures in thenerve terminal not the axon
- How does the rise in K external prevent the AP form entering the nerve terminal??
- Turns out: the terminals express a type of v-gated Na channel that is diff from the one on the axon
- Thes channels transit into the inactive state with just a slight depolarization in the membrane
○ The slight depolarization U would get by increasing K outside would be enough to inactivate these channels
○ So when AP reaches the terminal these channels are inactivated and cannot it cannot propagate and drops
○ These channels are not compartmentalized to the terminal...u have some just before the terminal
Then, u don’t have the signals for