The changes in the membrane potential in excitable cells are all ultimately brought about by the diffusion of ions across the plasma membrane. Diffusion is possible because there are marked differences in the intracellular and extracellular concentrations of a number of ions. The normal intracellular and extracellular ion concentrations for the major anions and cations in mammals are shown in the table below.
| Ion | [Intracellular] | [Extracellular] |
|---|---|---|
| Na+ | 12 mM | 145 mM |
| K+ | 155 mM | 4 mM |
| Ca2+ | 100 nM | 1.8 mM |
| Cl- | 4 mM | 115 mM |
Note that the concentrations of Na+, Ca2+ and Cl- are all much higher in the extracellular fluid whilst K+ has a much higher intracellular concentration. This situation is maintained by pumps such as the Na/K exchange pump that transports K+ into the cell and Na+ out of the cell against their concentration gradients using the energy derived from the breakdown of ATP.
Because these ions are dissolved in the aqueous solutions of the intracellular and extracellular fluids they are unable to move through the hydrophobic core of the lipid bilayer. Instead they move through specialised membrane spanning proteins known as ion channels. Many of these channels only permit the movement of one type of ion and are therefore said to be ion selective .
The movement of ions through many of these channels is carefully regulated by the opening and closing of a molecular gate and consequently these are known as gated channels. These gated ion channels come in a variety of flavours and we will deal with the major classes below.
(A) Voltage-gated Ion ChannelsThe characteristic feature of voltage-gated channels is that the state of the gate is determined by the membrane potential. These channels have a molecular sensor that measures the membrane potential and opens or closes the gate depending on its value. The diagram opposite shows the effect of changing the membrane potential of a neurone on the opening of different ion channels. Trace your cursor along the membrane potential graph to see voltage-depedence of the different channels. As we will see shortly, voltage-gated Na+ and K+ channels play an important role in the changes in the membrane potential associated with the action potential. |
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(B) Ligand-gated Ion ChannelsSome ion channels are gated by binding of chemicals to a receptor closely associated with the channel. The nature of the interaction between the chemical (ligand) and receptor enables a high degree of specificity in controlling ion channel opening. The diagram opposite shows a ligand-gated ion channel embedded in the plasma membrane of an excitable cell. Place your cursor over the bulb of the pipette to see how the channel is gated by the chemical in the pipette. Ligand-gated ion channels are important in a wide variety of physiological systems (including our acute sense of smell) and are implicated in a number of diseases as well as the actions of many therapeutic drugs. The changes in membrane permeability enabled by ion channels are also responsible for many forms of graded potentials as will see subsequently. |
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(C) Stretch-gated Ion Channels.The gating of some channels is regulated by the degree of stretch exerted on the membrane in which they are embedded. The mechanical deformation associated with the stretch produces a conformational (shape) change that opens the gate and allows ions to move through the channel. In the example opposite if you place the cursor over the membrane you can stretch it and see the effect that this has on channel opening. Channels of this type are involved in initiating graded potential associated with sensory stimuli (such as the skin deformation described in the previous section on frequency encoding). |
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In addition to these gated channels a small number of ion channels are described as resting channels (or passive channels) to indicate that they are not gated. Consequently these channels are open most of the time and are not significantly affected by the types of stimuli that open gated-channels. As we will see, these resting channels are very important in the formation of the resting membrane potential.