Animals - Nervous system: electrical signals, part I

November 14, 2002

1. The nervous system processes information in the form of electrical signals, i.e. rapid fluctuations of the electric potential (= voltage) across cell membranes. This sort of electrical signaling is also found in muscle cells and some other cell types, where the signals arise by the same mechanism.

• All cells have a a voltage difference or membrane potential between the cytoplasmic and extracellular sides of the cell membrane. The cytoplasm is negatively charged.
• Because neurons undergo rapid fluctuations of their membrane potential when signaling, we define the steady state membrane potential as the cell's resting potential.

2. As we have already discussed with respect to plant cells [see lecture, 9/12], membrane potentials arise from the activity of two distinct classes of membrane protein.

• Ion pumps are active transport proteins. Pumps utilize the energy released by ATP hydrolysis to move specific ion species across cell membranes.
• Ion channels are passive transport proteins. In essence, they are pores which allow specific small ion species to pass across the otherwise impenetrable lipid bilayer of the cell membrane. The direction of ion movement through an open channel is the sum of two factors:
  1. Diffusion causes an ion to flow down its concentration gradient, into or out of the cell.
  2. The electrical potential (or 'electrical gradient') between the cytoplasm and the extracellular fluid also drives ions across the membrane. Ions are attracted by opposite charge; repelled by the same charge.

3. In animal cells, the predominant ion pump is the Na/K pump, which actively transports Na⁺ ions out of cells and K⁺ ions into cells [see Campbell, Fig. 48.7].

• The activity of the Na/K pump causes the [Na⁺] outside the cell to be 10X greater than inside, and [K⁺] inside the cell to be 30X greater than outside.
• At any given time, a fraction of these transported ions are leaking back across the membrane, passing down their concentration gradients through their specific ion channels.
• It is this leakage of ions that is directly responsible for the electrical membrane potential. This can be shown by inactivating the Na/K pump with chemical poisons.

i. Inactivating the pump has no immediate effect on membrane potential since the ions continue to leak down their concentration gradients.

ii. However, ion leakage in the absence of pump activity slowly cancels out the concentration differences and eliminates the membrane potential.

4. To understand the origin of a cellular resting potential, it is useful to consider an artificial situation involving the flow of only one ion species.

• Imagine two liquid compartments separated by an artificial membrane that is permeable to K⁺ ions but impermeable to Cl^- ions. [Such a membrane is said to be 'semi-permeable'.]
• Imagine that Compartment #1 is filled with a 100 mM KCl solution, while Compartment #2 is filled with a 50 mM KCl solution [see Addendum A].
• At the starting time (t=0), there is no electrical potential across the membrane, and K⁺ ions will flow unimpeded down their concentration gradient - i.e. from Comp. #1 to Comp. #2. This ion flow has certain effects:
  1. It creates an electrical charge difference between the two sides of the membrane.
  2. This charge difference produces an electrical gradient that counteracts the concentration gradient and begins to impede the flow of K⁺ ions [see Addendum A].
  3. After sufficient time has elapsed, the two compartments reach an equilibrium condition in which the electrical gradient and the K⁺ ion concentration gradient are equal and opposite driving forces and there is no net ion flow.
• For any given ion concentration gradient, the term equilibrium potential refers to that (equal and opposite) electrical potential which is sufficient to counterbalance diffusion and maintain the equilibrium state, i.e. no net ion flow.

5. The concept of equlibrium potential can be extended to the cell membrane, which also separates two liquid compartments (cytoplasm and extracellular fluid). However, it is important to understand that the cell membrane is permeable to multiple ion species which can not all be at equilibrium at the same time.

• K⁺ ions are more concentrated intracellularly [due to the activity of the Na/K pump, see above] and the K⁺ equilibrium potential is approximately -85 mV.

• In contrast, Na⁺ ions are more concentrated extracellularly [also due to the activity of the Na/K pump], and the Na⁺ equilibrium potential is about +60 mV.

• In the resting cell membrane, the majority of open ion channels are K-channels, which dominate the electrical properties of the membrane. As a consequence the membrane is close to its potassium equilibrium and the resting potential is close to the K⁺ equilibrium potential.

• However, 1% of the open channels in a resting cell membrane are Na-channels, and they also contribute slightly to the resting potential.
  1. At the K⁺ equilibrium potential, Na⁺ ions are driven into the cell by both the electrical gradient and their concentration gradient.
  2. Hence there is a small but constant leak of Na⁺ ions into the cell, and this leak causes the membrane potential to be slightly more positive than the K⁺ equilibrium potential. For a typical animal cell, the resting potential is -70 to -80 mV.

6. To generate electrical signals, cell membranes open additional ion channels. This allows more ions to flow, which in turn causes the membrane potential to deviate from the resting potential.

• When the membrane potential of a cell becomes more positive, it is said to depolarize. When the membrane potential becomes more negative, it is said to hyperpolarize.
• One common electrical signal is the action potential, which involves a short-lived but strong depolarization of the cell membrane [see Campbell, Fig. 48.8c].
• A major component of the action potential is the opening of numerous Na-channels that were closed when the membrane was at its resting potential.

i. The rate at which Na⁺ ions flow into a cell is proportional to (1) the driving force (diffusion + electrical potential) multiplied by (2) the number of open Na-channels.

ii. When Na-channels open during an action potential, there is an increased flow of Na⁺ ions into the cell resulting in a depolarization of the cell membrane.

• Once all of the Na-channels have opened, they outnumber the K-channels (which were open at resting potential). When this happens, the membrane potential shifts to a value that is closer to the Na⁺ equlibrium potential than the K⁺ equilibrium potential. [The peak value of an action potential is about +30 mV; see Campbell, Fig. 48.8c.]
• In the next lecture, we will discuss the events that terminate the action potential and bring the membrane potential back down to the resting potential.

Learning goals

1. Learn the terminology of electrical membrane potentials: resting potential; depolarization; hyperpolarization.

2. Review the basic features of ion transport proteins. What is the difference between active and passive transport? What controls the movement of ions through an open ion channel?

3. What effect does the Na/K pump have on the distribution of Na⁺ and K⁺ ions inside and outside an animal cell? What role does this pump play in the production of the resting potential?

4. How does one define an ion's equilibrium potential? What is the relative contribution of the Na⁺ and K⁺ equilibrium potentials to the resting potential of a typical neuron?

5. Why does the opening of Na-channels during an action potential cause the cell membrane to depolarize?