|Composition of Intracellular and Extracellular Fluid
The cell membrane is the semipermeable barrier that separates the intracellular and extracellular fluids. These two compartments have every different ionic compositions.
(144 mM), low [K+]
(5mM) high [Cl
(15mM) and high [K+] (150mM); low [Cl-] and large [A---]
These concentration gradients are established by a combination of pumps and ion channels:
(a) the sodium-potassium pump uses energy from ATP to pump Na+ from the cell, and potassium in the opposite direction- from extracellular fluid to the interior of the cell.
(b) the cell membrane is selectively permeable to potassium ions, and potassium and diffuse freely though open channels.
Three ions of sodium move out of the cell and two potassium ions move in for every molecule of ATP consumed by the sodium-potassium pump, enduring that the internal sodium level is low, and potassium is high. Potassium ions however also redistribute themselves because of open potassium channels in the resting membrane. Whereas the membrane is rather impermeable to sodium ions.
Sodium is in high concentration in the extracellular fluid, but can't enter the cell in significant quantities even though theconcentration gradient across the membrane is high and the inside of the cell is negative, because the membrane is impermeable to sodium. Sodium channels exist in the membrane, but are closed; so no inward movement of sodium is possible in the resting neurone.
Passive movements of potassium ions
In contrast, potassium can move through open pores in the resting membrane that selectively admit potassium ions.
Potassium moves through open potassium channels, and there are two main forces that determine those movements:
(a) the concentration gradient for potassium, and
(b) the electrical gradient across the cell membrane.
The movement of an ion across the membrane depends on the concentration gradient for that ion, the electrical gradient, and the number of pores that are open to allow it to pass across the membrane.
The concentration gradient of potassium drives it OUT of the cell; but the electrical gradient across the cell membrane causes an INward movement of potassium.
When the fluxes of potassium In and Out are equal, there is a stable equilibrium - called an Electrochemical Equilibrium; and there is a mathematical relationship between the chemical gradient and the electrical gradient in that equilibrium.
The potential at which an equilibrium is reached for any concentration gradient is called the Equlibrium Potential. The mathematical equation that describes the equilibrium potential (E) for any ion is the Nernst Equation.
E (mv)= -58 log10[ A+ inside] / [A+ outside]
Equilibrium Potentials for Na+, K+, Cl-
Ions that can diffuse freely across the membrane satisfy the Nernst Equation; these ions pass through open channels in the membrane.
Ions that do not satisfy the Nernst Equation are not freely diffusible across the membrane, either because the membrane is impermeable to that ion, or because movements of that ion are regulated by other mechanisms, such as an active pump.
For the resting membrane, the transmembrane potential in nerves is about -70mv (70mv negative inside with respect to the outside of the cell).
The Nernst Equation predicts an equilibrium potential of about -70 mv for potassium and chloride, and + 140 mv for Na+
So the resting membrane appears to be permeable to K+ and Cl- and impermeable to Na+.
The Nernst Equation predicts that an elevated external potassium concentration will affect the membrane potential. As expected raised external potassium levels cause the cell to depolarise, which is why cardiac arrhythmias are common in this condition.
Similarly, low potassium concentrations in the extracellular fluid are associated with hyperploarisation of cells, which are less excitable.
The Goldmann Equation can be used to predict the transmembrane voltage predicted by ions that are in equilibrium across the membrane (in this case, Na+, K+ and Cl-:
Intracellular proteins are negatively charged at the normal pH of the intracellular fluid. Clearly, large molecules cannot move out of the cell, and their static charges attract positively charged ions into the cell. The charge on the intracellular proteins does not appear in the Nernst Equation, which describes the electrochemical equilibrium for potassium - this is the relationship closely resembles the electrical behaviour of the membrane.
Ohm's law: describes the relationship between voltage, current and resistance: V=IR
V(millivolts)=I (milliamps) x Resistance (Ohms)
Ohms' law is a very basic equation relating a potential gradient and current flow through a Resistor. The current flow depends on the voltage gradient and the resistance (I=V/R).
For biological membranes the voltage gradient is the transmembrane potential. The resistance depends on the number if open channels and their nature; and current flow occurs when ions flow through those channels as they open or close.
Changes in membrane potential occur when ions flow through newly opened ion channels.
The next chaper deals with the Action Potential. When the neurone becomes sufficienty depolariased, a threshold is reached that activates voltage-gated sodium channels, allowing them to open. At that point some (not many!) sodium ions flow through these channels into the neurone, driven by the sodium concentration gradient and the electrical gradient. A consequence of the entry of sodium is that the interior of the neurone becomes positive with respect to the outside: this potential change is the Action Potential.
Another example is if the membrane channels for chloride suddenly open (as a result of the administration of certain pharmacological agents), negatively charged Cl- ions flow into the cell and cause the membrane potential to become more negative - i.e. the neurone is hyperpolarised.
This happens when the neurotransmitter GABA activates ligand-gated chloride GABA-A channels, allowing Cl- into the cell. (However this has nothing to do with the generation of the action potential, but illustrates another mechanism that operates in some nerve cells).
Electrical Properties of the Cell Membrane :
The cell membrane consists of a fatty bi-layer that causes it to have electrical capacitance. When current flows in or out of the cell, the membrane behaves like a series of capacitors (lipid bilayer) in parallel with resistors (ion channels).
This arrangement means that when current is injected (say at a single synapse) the depolarisation recorded spreads around the local membrane (according to the length constant of the membrane) and takes time to occur (depending on the time constant of the membrane).
These local electrotonic potentials are able to sum both in time and space, and characterise the local subthreshold potentials seen in neurones when current flows across the cell membrane.