Physiology: Lecture 2 Flashcards
CASE #2
Paramedics respond to a call at a local, authentic Japanese restaurant. A patron is unconscious and cyanotic on the floor. The EMTs rapidly incubate and mechanically ventilate the patient. He is no longer cyanotic, but is severely hypotensive and unresponsive. Patients family report they had just finished dinner when he complained of numbness and tingling of his face. This progressed to an inability to breathe (dyspnea) and finally unconsciousness. Waitstaff performed the Heimlich, nut no foreign body was ejected. Patient is taken to the ER. He is continued on ventilation and is given IV saline to boost his blood pressure. After 24 hours, the patient recovers and is released in perfect health the next day.
What is your diagnosis?
What physiological processes were altered?
- Diagnosis: Blowfish toxin
- Physiologic processes that were altered: membrane and action potential were inhibited by the blowfish toxin, affecting Na from crossing the membrane, stopping the action potentials
Permeability of cell membrane?
Selective permeable; some things (small, non-polar molecules, steroids, oxygen, etc.) can diffuse through membrane
Why can most solutes in the body not cross the membrane?
They are large and/or charged
How is conductance carried out for the solutes that are not able to cross the membrane?
By use of transport proteins and ion channels
The amount of solutes that are able to cross the membrane is based on what?
Number and activity of these proteins
What are ion channels?
Small holes that allow specific size/charge of ion to cross
What is conductance based on within ion channels?
The number of channels that aren’t ‘open’
What are the two characterizations of ion channels and ionic movement?
- SPECIFIC to ionic size and charge
- Flow depends on number open (channels)
What’s it called if a sodium channel can exclude a calcium/potassium ion due to different molecule size?
Size exclusion
What’s it called when the interior of the channel is lined with charged amino acids, preventing like ions from crossing it?
Charge exclusion
Characteristics of leak channels
- always open
- some K channels and Cl channels
*K is very important to remember
Characteristics of gated channels
- Closed until stimulus opens
- Ligand (drug or hormone or neurotransmitter that binds to receptor on cell surface), 2nd messenger, voltage, mechanical, light, etc.
Channels that remain closed until the proper ligand (drug, hormone, chemical) binds, but remains open as long as the ligand is around, and closes when it is removed.
Ligand gated channel
Nicotinic receptors in skeletal muscle’s neuromuscular junction are examples of what? Explain what they do.
Ligand gated channels
They bind ACh, allowing Na (mostly) and K (little) to flow down gradients [transmits signal from nerve to muscle]
Channels that remain open as long as the 2nd messenger is around, but close when it’s removed
2nd Messenger Gated channel
What is made in a 2nd messenger channel until the receptor is no longer stimulated?
2nd messenger
Ca2 channels in smooth muscle cells are examples of what type of channel? Explain what happens
2nd Messenger gated channel
Angiotensin II binds to its receptor, causing production of IP3, which binds to and opens Ca2 channels (InsP3R).
Channels that remain closed until the membrane potential reaches a specific value, but remains open depending on the membrane potential and channel properties
Voltage gated channel
The Sodium Channel (Nav) in muscles is an example of what kind of channel? What happens in it?
Voltage gated channel
Once the membrane potential gets above a certain point, they open. When it reaches a 2nd set point, they close.
QUESTION:
Which type of channel would have the most rapid effect on ionic flow?
Ligand gated because you are going to open up a channel
QUESTION:
Which type of channel could lead to a more varied cellular response?
2nd messenger gated
What do ions do when they move down a concentration gradient?
They generate a current
What is the diffusion potential?
Only moves until the charge changes, not big change in concentration; measured in mV
The potential difference (charge) required to stop ionic movement [ions moving down concentration gradient to create a diffusion potential continues until they reach this]
Equilibrium potential
What do ions move in response to in the equilibrium potential?
Concentration AND Charge
What generates an electrical potential? What’s it the basis for?
-Movement of charged particles (relatively few ions have to move to make a charge difference across a membrane)
-This is the basis for resting membrane potential and the nervous system.
(This does NOT create an isotonic or hypertonic solution)
What does the Nernst equation determine?
The Equilibrium potential per ion
(-2.3RT/zF)log(Ci/Co) = ? = -60/z log(Ci/Co)
Nernst equation Z = charge of ion Ci = concentration inside the cell Co = concentration outside the cell *Sign is with respect to the cell interior (can infer sign based on where ion usually is and its charge)
What is the equilibrium potential for the major ions (Na, K, Cl, and Ca)? Eq = -60/z log (Ci/Co); resting potential is usually ~ -70mV
E(Na) = +65 mV E(K) = +120 mV E(Cl) = -85 mV E(Ca) = -90 mV
[Ca wants to go into the cell more than Na]
[K wants to leave the cell (+ charge wants out)]
[Cl wants to go inside the cell (- charge wants in)]
What is the driving force in the Nernst equation?
How much the membrane wants to move;
mV = Em - Ex
Em = actual membrane potential
Ex = equilibrium potential
What is the driving force of potassium?
mV = Em - Ex
mV = Em - Ex mV = -70 - (-85) = 15
What is the driving force of Na?
mV = Em - Ex
mV = Em - Ex mV = -70 - 65 = -135
What does the Nernst equation account for?
ALL ionic concentration gradients and membrane permeability; and you get the Resting Membrane Potential (RMP) [Goldman Eqn or chord eqn]
**Channels have importance in determining ionic flow
What is the resting membrane potential (RMP)?
Charge difference across cell membranes due to concentration gradients of permeant ions; each ion tries to push the RMP towards its own Eq potential
Which part of cell is considered negative when talking about the resting membrane potential (RMP)?
Inside of cell is considered negative compared to outside
What is the range of the resting membrane potential (RMP)? What tissue is changing?
-20 to -100 mV
Excitable tissue (muscles and nerves) can rapidly change the RMP to send signals and start contraction.
About -70 in neurons; -90 in skeletal and cardiac muscle
QUESTION:
Increasing permeability of _______ to 100% would likely result in the greatest change in resting membrane potential?
Calcium because the equilibrium potential of Ca is +120 (higher than the rest of the major ions)
Rapid changes in membrane potentials, consisting of depolarization from and repolarization to resting membrane potential (RMP)
Action potentials
Characterizations of action potentials
- All ‘normal’ AP’s from a cell type a similar (all ventricular myocytes look the same, but are different from cardiac node cells)
- All AP’s are propagated (move from one site to the next and are nondecremental
- An AP either occurs or it does not (all or none principle; If membrane reached specific voltage [threshold…usually is the opening of Na channels] then an AP will occur)
What are the 7 stages of the action potential?
1) At rest - RMP
2) Local depolarization (membrane moves closer to 0mV)
3) Threshold (about 60mV; Point at which AP has to occur)
4) Overshoot (interior becomes (+) relative to outside)
5) Repolarization (membrane begins to move back towards 0 and negative)
6) Hyperpolarization (membrane becomes MORE negative)
7) At rest (RMP is re-attained)
Charge going away from 0
Polarization
Charge going toward 0
Depolarization
At rest, what is the voltage of RMP, what’s it maintained by, and what is necessary for the polarization to remain at RMP
- -70mV
- maintained by K leak currents (eq = -85)
- Na-K ATPase is necessary (3 Na out; 2 K in; inside becomes more negative; also maintains large K gradient so small flux can occur and generate the RMP)
Where are sodium and potassium located, in relation to the cell during RMP?
Lots of Na outside the cell (+1 charge outside cell)
Lots of K inside the cell (+1 charge inside cell)
What happens to the cell during RMP if you close/open K channels?
- Close: Inside of cell becomes more negative
- Open: Inside of cell becomes more positive
Is the RMP stable is all cells?
No; It is stable in MOST cell types, but unstable in rhythm generating cells (ex: cells in the heart and in cells moving through the intestines)
Major contributor to the RMP?
K current through leak channels
What happens during local depolarization to the membrane potential?
- Stimulation occurs - usually ligand gated Na channel
- Local membrane moves closer to 0mV
- Stimulated
What happens during local hyperpolarization to the membrane potential?
- Stimulation occurs - usually ligand gated Cl Channels
- Local membrane becomes MORE negative
- Inhibited
Is there a change in the membrane potential if you open enough nicotinic channels?
Yes
At what voltage is threshold at?
~ -60mVish
What happens if local depolarization reaches threshold?
- AP HAS to occur
- Voltage gated Na channels open (these are responsible for the depolarization of AP)
Describe the 2 types of voltage gated sodium channels
- Activation gate (outside; closed at RMP) - opening of Na channels at threshold, allowing for depolarization to happen
- Inactivation gate (inside; open at RMP) - closing of Na channels after overshoot
What is required for an action potential? If it’s blocked, what happens?
- Required = Voltage gated sodium channels
- If blocked = no AP will occur - paralysis will happen (if you have tetrodotoxin or take lidocaine)
What happens to the membrane potential during overshoot?
- Getting back to where only the leak channels are open, and we are happy again
- Due to rapid influx of Na
- Usually peaks at +35mV
- Inactivation gates close, no more Na
- Voltage gated K channels open at peak, but since there’s only 1 gate, it is much slower to close…this leads to the repolarization = losing positive charges and blocked by tetrathylammonium (TEA)
What is accommodation, when referring to membrane potentials?
When the gate doesn’t open in time
What happens during repolarization of the membrane potential?
- Na conductance slows (channels close)
- K conductance rises (channels open)
- More positive charges leave the cell (K out)
What happens during hyperpolarization of the membrane potential?
- Membrane becomes MORE negative than RMP
- Will hyperpolarization closer to the K equilibrium point (close to -65mV)
How is RMP re-established?
- K gates close (Leak channels and Na-K ATPase)
Summary of ionic basis for the AP
- At rest - RMP (K flux through leak channels)
- Local depolarization (stimulation occurs - ligand gated Na channels)
- Threshold (~ -60mV; Na channels open)
- Overshoot (Na flux)
- Repolarization (Na slows; K rises)
- Hyperpolarization (More K leaving)
- At rest (RMP is re-attained due to K leak)
What are RMP and AP’s based on?
Ionic gradients (at rest, only open channels are K so RMP is sensitive to alteration in plasma levels)
What is it called when you have too much K, less of a gradient because you have a more positive RMP (hypopolarizes)?
Hyperkalemia
What is it called when you have don’t have enough K, and more of a gradient because you have a more negative RMP (hyperpolarizes)?
Hypokalemia
What happens during accommodation due to hyperkalemia?
- Slowly depolarizing can stop AP’s from being generated
- Occurs due to inactivation gates closing before activation opens (No Na, No AP)
- Can be the result of persistent hyperkalemia (decreased gradient, raises RMP towards 0; No AP = paralysis of muscles = death)
QUESTION: Which of the following could be a consequence of acute hyperkalemia? A) Decreased threshold voltage B) Increased threshold voltage C) More steep repolarization slope D) Less steep repolarization slope
- D) Less steep repolarization slope
**K moving out, so you can’t move any more out…making it less steep
QUESTION: What affect would hypernatremia have on the RMP? A) Large hyperpolarization B) Large hypopolarization C) No change
- C) No change
**At rest, there are no Na channels open, so there is no change
What are action potentials used for? When must the time be for them to carry out their jobs?
- Used to send information
- Must be times of silence or refractory periods
What are refractory periods due to?
- Due to cells inability to depolarize again (channels not reset)
- They are the amount of time the cell has altered functions
Period when there is no AP and the activation gate of Na is not closed
Absolute Refractory Period
“I don’t care how many signals you send…nothing is going to happen because no Na gates are open”
??????
Period when you need a greater than normal stimulus and the K flux hyperpolarizes the cell, making it harder to get to threshold
Relative Refractory Period
“Can get AP, but it takes more input (need greater stimulus)”
What is excitability?
How easy it is to get a response
