Membrane potential is the potential difference across the plasma membrane. Membrane potential is essential to spread electrical signals called nerve impulses across every cell’s plasma membrane. Neurons communicate through changes in the electrical properties of the cell membrane that travel from one cell to another. Membrane potential is maintained as such that the side of the membrane exposed to the cytoplasm is the negative, and the side exposed to the extracellular fluid is the positive. The inside of the cell is more negatively charged in relation to the outside because of three factors:-
- Large molecules like proteins and nucleic acids which are negatively charged are more abundant inside the cell and cannot diffuse out. These molecules are called fixed anions.
- The sodium-potassium pump brings only two potassium ions (K+) into the cell for every three sodium ions (Na+) it pumps out. In addition to contributing to the electrical potential, this also establishes concentration gradients for Na+ and K+.
- Ion channels allow more K+ to diffuse out of the cell than Na+ to diffuse into the cell.
Na+ and K+ channels in the plasma membrane have gates, portions of the channel protein that open or close the channel’s pore. In the axons of neurons and in muscle fibers, the gates are closed or open depending on the membrane potential. Such channels are therefore known as voltage-gated ion channels.
Table of Contents
- Resting Membrane Potential
- Action Potential
Resting Membrane Potential
- In majority of cells, the permeability of ions through the cell membrane is constant, and the net negativity on the inside of the cell remains constant.
- The plasma membranes of muscle and neurons, however, are excitable, this is so because, the permeability of the ion channels in the plasma membrane of these cells can be altered by various stimuli.
- When a neuron is not being stimulated, it maintains a resting membrane potential (RMP) which is about –70 millivolts (–70 mV or 0.07 volts). The negative sign indicates that the inside of the cell is negative with respect to the outside.
Why Resting Membrane Potential is -70mV?
We know that the resting membrane potential is –70 mV because of an unequal distribution of electrical charges across the membrane. But why –70 mV rather than –50 mV or –10 mV? To understand this, we need to remember that there are two factors involved in establishing the resting membrane potential:
- Asymmetric distribution of ions across the plasma membrane (i.e., ion concentration gradients); and ions respond to concentration gradients by moving from an area of high concentration to an area of lower concentration.
- Specific ion channels in the plasma membrane. K+, Na+, and Cl− channels are the most important channel types for most cells; however, there are many cells in which other channels are important as well.
Asymmetric distribution of ions across the plasma membrane
Asymmetric distribution of ions across the plasma membrane creates two forces chemical gradient and electrical gradient that are responsible for generating resting membrane potential.
- It is to be noted that ([K+]inside the cell> [K+]outside the cell), that establish K+chemical gradient across plasma membrane.
- K+-selective channels in the plasma membrane, tend to move K+ ions from cytoplasm to extracellular fluid because of this chemical gradient.
- Cl− cannot follow because the channels are highly selective for K+ and do not allow Cl− to pass. Therefore, movement of K+ from inside the cell to outside the cell leads to charge separation across the membrane.
- Every K+ ion that moves from inside the cell to outside the cell creates a net positive charge to the extracellular side of the plasma membrane and, simultaneously, leaves behind a net negative charge on the intracellular side of the membrane. This charge separation leads to the generation of an electrical gradient (i.e., electric field), which forms the basis for the establishment of the membrane potential.
- When the electrical gradient exactly balances the chemical gradient, K+ is said to be at electrochemical equilibrium. Based on the intracelluar and extracellular concentrations of K+ used in this example, the final (i.e., equilibrium) value of the membrane potential is about −90 mV (intracellular side negative with respect to the extracellular side).
Cl− cannot follow K+ Ions path because the channels are highly selective for K+ and do not allow Cl− to pass. ([Cl−]inside the cell> [Cl−]outside the cell)
Small amount of sodium ions diffuse from ECF to Cytoplasm. ([Na+]outside the cell>[ Na+]inside the cell)
Equilibrium Potential & Nernst Equation
- The Nernst equation describes the electrochemical equilibrium (When the chemical and electrical gradients are equal in magnitude, the ion is said to be in electrochemical equilibrium) distribution of an ion between two compartments that are separated by a membrane that contains channels selective for that ion.
- At equilibrium, this potential difference is described by the Nernst equation, and is referred to as the equilibrium potential (Veq.) or Nernst potential for that ion. The Nernst potential for any given ionic species is the membrane potential at which the ionic species is in equilibrium; i.e., there is no net movement of the ion across the membrane.
- The below image shows the nernst equation
- The Nernst equation allows us to quantitatively calculate the equilibrium potential that will be established across the plasma membrane based on the valence and concentration gradient of respective ion (provided that only specific channels are present).
- If two or more ions contribute to the membrane potential, the Nernst potential no longer yields the Vm. In this case, use the Goldman-Hodgkin-Katz (GHK) equation (image below) to caculate Vm.
Specific ion channels
The voltage at which the influx of any ion equals the efflux of ion is called the equilibrium potential.
Non-Gated K+ channels
- The positively charged ions, called cations, outside the cell are attracted to the negatively charged fixed anions inside the cell.
- However, the resting plasma membrane is more permeable to K+ than to other cations, so K+ enters the cell.
- Other cations enter the cell, but the leakage of K+ into the cell has the dominant effect on the resting membrane potential, due to presence of large number of non gated K+ channels in the cell membrane.
- For potassium, the equilibrium potential is –90 mV. At –80 mV, K+ will diffuse out of the cell and at –100 mV K+ will diffuse into the cell.
Na+ Leaky Channels
- Membrane is also slightly permeable to Na+, and its equilibrium potential is +60 mV
- Membrane is also permeable to Cl–, and its equilibrium potential is -70 mV.
- In addition to the electrical gradient driving K+ into the cell, there is also a concentration gradient established by the sodium-potassium pump that is driving K+ out of the cell.
If K+ were the only cation involved, the resting membrane potential of the cell would be –90 mV. However, the membrane is also slightly permeable to Na+, and its equilibrium potential is +60 mV. The effects of Na+ leaking into the cell make the resting membrane potential less negative. With a membrane potential less negative than –90 mV, K+ diffuses into the cell, and the combined effect bring the equilibrium potential for the resting cell to –70 mV.
- If stimulus is so small that the plasma membrane is depolarized slightly, but soon decays back to the resting membrane potential.
- These small changes in membrane potential are called graded potentials because their amplitudes depend on the strength of the stimulus.
- Graded potentials can be either depolarizing or hyperpolarizing and can add together to amplify or reduce their effects, just as two waves add to make one bigger one when they meet in synchrony or cancel each other out when a trough meets with a crest.
- The ability of graded potentials to combine is called summation.
- Once a particular level of depolarization is reached (about –55 mV in mammalian axons), however, a nerve impulse, or action potential, is produced.
- The level of depolarization needed to produce an action potential is called the threshold.
Steps of generation of action potential
- A depolarization that reaches or exceeds the threshold Na+ gated channels open first.
- The rapid diffusion of Na+ into the cell shifts the membrane potential toward the equilibrium potential for Na+ (+60 mV).
- This part of the action potential appears as the rising phase of a spike (figure above).
- The membrane potential never quite reaches +60 mV because the Na+ channels closes.
- The action potential thus peaks at about +30 mV. Opening the voltage gated K+ channels allows K+ to diffuse out of the cell, repolarizing the plasma membrane.
- This repolarization of the membrane appears as the falling phase of the action potential.
- In many cases, the repolarization carries the membrane potential to a value slightly more negative than the resting potential for a brief period because K+ channels remain open, resulting in an undershoot.
- The entire sequence of events in an action potential is over in a few milliseconds.
- Action potentials have two distinguishing characteristics.
- First, they follow an all-or-none law: each depolarization produces either a full action potential, because the voltage gated Na+ channels open completely at threshold, or none at all.
- Secondly, action potentials are always separate events; they cannot add together or interfere with one another as graded potentials can because the membrane enters a brief refractory period after it generates an action potential during which time voltage-gated Na+ channels cannot reopen.
- The production of an action potential results entirely from the passive diffusion of ions.
- However, at the end of each action potential, the cytoplasm has a little more Na+ and a little less K+ than it did at rest.
- The constant activity of the sodium-potassium pumps compensates for these changes.
- Thus, although active transport is not required to produce action potentials, it is needed to maintain the ion gradients.
Propagation of Action Potentials
- Although we often speak of axons as conducting action potentials (impulses), action potentials do not really travel along an axon—they are events that are reproduced at different points along the axon membrane. This can occur for two reasons:
- Action potentials are stimulated by depolarization, and
- An action potential can serve as a depolarization stimulus
- Each action potential, during its rising phase, reflects a reversal in membrane polarity (from –70 mV to +30mV) as Na+ diffuses rapidly into the axon.
- The positive charges can depolarize the next region of membrane to threshold, so that the next region produces its own action potential.
- Meanwhile, the previous region of membrane repolarizes back to the resting membrane potential.
- This is analogous to people in a stadium performing the “wave”: individuals stay in place as they stand up (depolarize), raise their hands (peak of the action potential), and sit down again (repolarize).
- Nerve Impulse Propagation are of two types
Continuous Conduction (Slow)
Occurs unmylinated axon but ion flow through voltage gated channel gradually (depolarization & repolarization in PM).
Saltatory Conduction (Fast)
- Action potentials are conducted without decrement (without decreasing in amplitude); thus, the last action potential at the end of the axon is just as large as the first action potential.
- The velocity of conduction is greater if the diameter of the axon is large or if the axon is myelinated.
- Myelinated axons conduct impulses more rapidly than non-myelinated axons because the action potentials in myelinated axons are only produced at the nodes of Ranvier.
- One action potential still serves as the depolarization stimulus for the next, but the depolarization at one node must spread to the next before the voltage-gated channels can be opened.
- The impulses therefore seem to jump from node to node (figure above) in a process called saltatory conduction.
- When action potential begins excitable cell unable to generate another action potential in response to normal threshold stimulus that period of time called as refractory period.
- Refractory period limits the no of action potential
Absolute Refractory Period
Strong stimulus cannot initiate next another action potential because it overlap with period of voltage gated Na+ channel activation & inactivation. Inactivated Na+ cannot open until close
Relative Refractory period
Can be generate other action potential when more stimulus than normal provided. It overlap with K+ channel are open.