Excitability of cells and tissues is a basic function of life. Also known as irritability, it is the ability of cells to respond to stimuli. Excitability is necessary for the functioning of nerves, muscles, and hormones, among other things. The basis for the excitability of cells is their ion distribution, and the distribution of ions and molecules is determined by transport mechanisms associated with their plasma membrane structure. This structure permits and regulates various forms of ionic and molecular transport.
Slide 1 illustrates various forms of transport across a selectively permeable membrane. They include passive mechanisms such as diffusion of ions and small molecules through protein channels, diffusion of fat-soluble molecules through the phospholipid matrix, and specialized carrier mechanisms which allow the kinetic energy of molecules, for example glucose, to power diffusion across a membrane with the aid of a carrier. (Slide 2). All of these passive mechanisms can only allow diffusion of ions and molecules down their concentration gradient. They play important roles in the electrical potential exhibited by cells. Facilitated diffusion will be seen later to play a role in the transport of molecules such as glucose, for example, into and out of many cells.
Slide 1 also illustrates active transport mechanisms, which can move ions and molecules against their concentration gradient. The Sodium-Potassium pump is a well-known example and is important in establishing unequal distributions of these ions. Another example you will encounter is active co-transport (Slide 3) in which a molecule is moved against its concentration gradient utilizing the energy produced by the gradient established by the Na+/K+ pump. Such transport is important in the absorption of monosaccharides and amino acids in the GI tract. In this way by pumping Na+ out of the basal end of the cell, glucose can be brought in through the apical end of the cell [diagram].
The Na+/K+ pump is called an electrogenic pump because it produces the unequal distribution of Na+ and K+ ions which results in the concentration gradient responsible for the resting membrane potential. As Slide 6 illustrates, this pump has three attachments on the intracellular side for Na+ and 2 attachment sites on the extracellular side for K+ ions. On the inside of the pump protein is located an ATPase. When the sodium ions and potassium ions attach to the appropriate sites on the pump protein, the ATPase is activated and hydrolyzes ATP. The resulting energy release produces a conformational change in the pump protein molecule which moves the Na+ to the extracellular side and the K+ to the intracellular side of the plasma membrane. This produces the concentration gradient observed for these ions and the unequal charge distribution results in a polarized membrane. [See also Marieb5th Figure 11.9]
These ions tend to diffuse across the plasma membrane down their concentration gradient, particularly the potassium ions. This diffusion takes place through both non-selective (Slide 4) and selective (Slide 5) ion channels. The non-selective channels are much more permeable to potassium than to sodium. There are selective channels for each ion but many more for potassium than for sodium. The result is that K+ ions are about 100X more permeable than Na+ ions.
The actual resting membrane potential (RMP) is the result of the passive and active forces described above: First and primarily the diffusion of potassium ions down its concentration gradient; second the sodium-potassium pump itself; thirdly the diffusion of ions other than potassium. The Nernst Equation (Slide 7) expresses the electrical potential produced by a given ion. Just considering potassium which has a concentration inside the cell of 150 mM and a concentration outside the cell of about 5 mM (according to Marieb, Figure 11.8), this produces a potential of -67 mv across the plasma membrane. The Na+/K+ pump produces about another -3 mv for an observed RMP of around -70 mv. For muscle and nerve cells the observed RMP can range from about -50 to about -90 mv.
Having a membrane potential in itself does not make the membrane excitable. What makes it excitable is the possibility of depolarization or reversal of this potential. This occurs as the result of gated channels. Gated channels have gates which can open or close to allow particular ions to pass through the channel. They respond to a stimulus such as a voltage change, chemical, mechanical, or other stimulus which causes them to open. In the units on muscle physiology and neurophysiology we will discuss chemically-gated channels and voltage-gated channels found in muscle cells and neurons which are responsible for the depolarization important in the function of these cells.
Chemically-gated ion channels respond to a chemical such as a neurotransmitter, e.g. acetylcholine (ACh), (Slide 8). On the cell membrane of a skeletal muscle cell ACh causes the gates of Na+ channels to open, allowing Na+ ions to enter the cell. Because it opposes the existing polarization of ions by letting positive ions into the cell, we say it depolarizes the membrane. Many such channels opening at once can produce a significant membrane depolarization. Membrane depolarization in turn causes opening of voltage-gated channels (Slide 9) which are sensitive to reduced membrane potential. When a certain amount of depolarization occurs, called the threshold, it results in all of the voltage-gated channels opening and produces an action potential. Slide 10 shows the sequence of events as gates of the Na+ and K+ channels open and close in sequence to produce the wave of depolarization called the action potential. The action potential will be discussed at greater length in the nervous system.