Flashcards in Resting Membrane Potential Deck (28):
What are the principal players in the maintenance of steady-state trans-membrane gradients for Na+, K+, and Ca2+?
primary active ion pumps
Of particular importance to the bioelectric properties of cells are what tow gradients?
- the outwardly directed gradient for K+
- the inwardly directed gradient for Na+
*both of these are developed and maintained through the activity of the Na,K-ATPase
So let's say you have permselective membrane for K+. You have 100 mM [K+] inside cell, 10 mM outside cell. You also have 10 mM Na+ inside cell, 100 mM outside cell. Describe the movement of K+.
K+ gradient causes K+ to leave the cell. This leaves a negative charge inside the cell (because of anions left in the cell that the membrane is not permeable for). This negative charge causes K+ to be pulled back into the cell. and gradually increases to a level that exactly balances the chemical force, resulting in an 'equilibrium' condition.
The equation that describes this balance of electrical and chemical forces is called the Nernst equation.
What equation describes the balance of electrical and chemical forces?
The Nernst Equation
E_k = -R*T/(z*F) * ln ( [K+]in/[K+]out )
E_k = -61.5 mV * log_10 ( [K+]in/[K+]out )
E_k = equilibrium potential difference (PD) which exactly opposes the chemical energy of the chemical gradient
[K+]in/[K+]out = the chemical gradient
z = valence of the ion question (+1 for K+)
R, gas constant; T, temperature, F, Faraday constant
Any manipulation that reduces the K+ gradient (i.e. by either decreasing intracellular [K+] or increasing extracellular [K+]), will ______ the equilibrium potential for K+.
If there is less energy in the chemical gradient, it will take _____ energy in an electrical gradient to 'balance' it.
What does the Goldman-Hodgkin-Katz Constant Field equation (Goldman equation) represent?
the more physiologically realistic case in which the membrane shows a finite permeability to the three major players (K+, Na+, Cl-)
Most channels display "gating" (the conformational change of the channel protein associated with "opening"). What are the five types of gating?
- voltage gated
- ligand gated
- second-messenger gated
- mechanically gated
Voltage gated channels
changes in membrane potential (typically, depolarization) induce channel opening (by means of conformational changes of an amino acid sequence in the channel protein, a 'voltage sensor)
Ligand gated channels
the (non-covalent) binding of an external "ligand" (e.g. neurotransmitter) to a receptor site on the external face of the channel results in a conformational change of the channel protein that opens the channel
Second-messenger gated channel
modification of the cytoplasmic face of channel, via second messenger-mediated pathways, results in channel opening
- ex: non-covalent binding of a small molecule (similar to ligand gated)
- ex: covalent modification (e.g. phosphorylation)
Mechanically gated channel
physical deformation of the membrane ('stretch') results in channel opening
these channale proteins are usually tethered to cytoplasmic elements that 'tug' on the protein when stretched
changes in current flow through these channels is not due to conformational changes of the protein itself (but by other mechanisms...)
Channels generally show some degree of ____
Most channels can have their behavior altered through the influence of a modifying agent. These can be drugs or toxins, but also include physiologically important molecules.
Toxins of interest:
- Tetrodotoxin (TTX)
Where are these toxins often found and what is their influence?
- basis of puffer fish poison
- blocks an important class of gated Na channels
- in venom of Banded Krait snake
- binds to and blocks the nicotinic acetylcholine (ligand)-gated channel of the neuromuscular junction
Some gated channels also show some degree of _____
(i.e., shortly after opening, they close again, despite the continued presence of the stimulating agent; this is important for some channels, e.g. voltage-gated Na-channel)
What types of ion channels have we found for Na+ ions?
- ligand gated channels
What types of ion channels have we found for K+ ions?
- non-gated channels (found in plasma membrane of all animal cells that are responsible for setting the 'resting' electrical state of the cell)
- voltage-gated channels (delayed-rectifiers) (work in concert with voltage gated Na+ channels to produce the profile of electrical activity associated with the 'action potentials' of so-called "excitable cells," nerve cells, skeletal, cardiac, and smooth muscle cells)
- non-gated and second messenger-gated K-channels in epithelial cells that play an important regulatory role in salt and water transport
What types of ion channels have we found for Cl- ions?
- cystic fibrosis transmembrane conductance regulator (CFTR) - second messenger-gated; activation of CFTR involves both cAMP and ATP
- voltage-gated (CLC-1) - critical role in skeletal muscle
- ligand-gated in central nervous system (GABA or glycine is required ligand); important for inhibitory events in nervous system
What types of ion channels have we found for Ca2+ ions?
- ligand gated
- second messenger gated
Which ions are concentrated more on the outside vs the inside of the cell?
Na+ and Cl-
K+ has a higher concentration on the inside of a cell
What is one process that can typically keep ions from reaching equilibrium across membrane?
What makes the interior of animal cells electrically negative with respect to the external solution?
combination of an outwardly-directed K-gradient (the product of Na,K-ATPase activity) and a high resting permeability to K+
*note, the finite permeability of the membrane to Na+ and Cl- prevents the potential from ever actually reaching the Nernstian K potential
What are examples of situations in which membrane permeability to Cl- (as defined by Cl channels) is very important?
- Cl- permeability is modulated as one means to influence synaptic transmission
- congenital defects in the Cl- channel found in skeletal muscles (CLC-1) can have a profound influence on the excitability of these cells
Change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization.
What can cause hyperpolarization?
Increased efflux of K+, or increased influx of Cl-
(inhibited by causes of depolarization)
positive-going change in a cell's membrane potential, making it more positive, or less negative, and thereby removing the polarity that arises from the accumulation of negative charges on the inner membrane and positive charges on the outer membrane of the cell