The Ionic Basis of the Membrane Potential

Introduction

The membrane potential (V_m) maintained by cells is one of their most notable and important features. All cells exhibit a membrane potential, at the expense of considerably energy required to maintain the charge separation across the membrane that produces the potential. Then, of course, there is the complexity in terms of the ion pumps, ion channels, etc. that had to be evolved to support the cell’s ability to generate the membrane potential and to all the cell to change V_m when appropriate or necessary.

Just to hint at the importance of V_m in cell function, here is an eclectic, very incomplete, listing of cell processes that depend on – or at least involve – membrane potentials and changes therein:

· Contraction of muscle fibers of all types – movement (skeletal muscle fibers), pumping of blood by the heart (cardiac muscle fibers), shunting of blood to different parts of the vascular system (smooth muscle fibers), and peristaltic movement of ‘food’ through the digestive tract (smooth muscle fibers) – just to mention a few examples – all depend directly on membrane potentials.

· Information transfer and processing by the nervous system

· Stimulus transduction by sensory receptors

· Regulation of the cardiovascular system by the Autonomic Nervous System

· Response of the immune system to invading microorganisms.

· Fertilization – in many species, fusion of a sperm with the egg can only occur if the egg’s V_m is sufficiently negative; otherwise, the ‘binding proteins’ in the oocyte’s and the sperm’s membrane are not in the proper conformation for binding to occur. As soon as one sperm fuses with the egg, a depolarization of the egg’s membrane takes place, the result of increased g_Na+. The depolarization makes it impossible for any more sperm to bind to the oocyte and fuse with it. This is an important adaptive mechanism for preventing polyspermy, the fertilization of a single oocyte by more than one sperm.

· Phagocytosis and destruction of bacteria by white blood cells.

· Invasion of hosts by bacteria such as the causative agent of cholera (Vibrio cholerae) – the bacteria’s V_m is considerably more negative (» -150 mV) than that of its host cells. When the bacterium comes in close proximity to a host cell, the resulting decrease in the bacteria’s V_m triggers the expression of literally hundreds of genes whose products, termed “virulence factors”, are necessary for successful attack of the host cell..

· Entry of bacterial toxins (e.g., pertussis toxin) into their target cells. – the resting V_m characteristic of eukaryotic cells

· Hormone secretion by endocrine glands (e.g. insulin by b-cells in the pancreas).

· Defensive responses of plants to attack by pathogenic fungi.

· Entry of bacteriophages into bacteria.

This list could easily be extended to include myriad examples, but you can see that many of the physiological processes you’ll be studying during this course (and many more you won’t!) directly or indirectly involve V_m.

Given the ubiquity and importance of V_m, it is essential for biologists to have a good understanding of how it’s produced and how it can be changed. The purpose of this simulation is to let you investigate some of the factors that influence the magnitude of V_m. Once you’ve worked through the accompanying exercises, you will have developed a firm grounding in the ionic basis of the membrane potential, one that will serve you in good stead during future study of physiology.

What Does The Membrane Potential Simulation Allow You To Do?

This simulation allows you to investigate the effects of Na⁺ and K+ on membrane potential (V_m). Specifically, the simulation provides controls that let you:

1. change the concentration gradient for one or both ions by changing the external and/or internal [Na⁺] and [K⁺], and

2. vary the conductance (g_m) for each of the ions.

After you make these changes, the simulation calculates V_m based on the new values that you've specified for [Na⁺], [K⁺], and g_m.

What Does The Membrane Potential Simulation Display?

When you first start the simulation, depending on the size of your monitor’s screen and the particular browser you’re using, you’ll see a display that looks similar to this:

Most of the display's area is taken up by a set of axes on which membrane potential (V_m) will be graphed as a function of time (in milliseconds, ms). To the right of these axes is a control panel. The top part of this panel displays four sliders that allow you to change the concentration gradients for Na⁺ and K⁺ (by changing their external and/or internal concentrations). Below those four sliders are two more sliders that allow you to change the conductance for Na⁺ or K⁺.

You initiate a simulation run by clicking on the "Go" button. However, any changes you have made in ion concentrations and/or conductance are not applied until t = 1 ms after the simulation commences. Thus, when you click the "Go" button, you will first see the resting membrane potential calculated from the default values for the concentrations and conductance. At t = 1 ms, the new parameter values you have specified are applied and the graph illustrates the time-dependent change in V_m as it approaches the new V_m that your values for ion concentrations and conductance have established across the plasma membrane.
At the end of each simulation run, the numerical value of the new V_m is displayed to the right of the line.

The graph for each subsequent run is displayed using a different line color, and a legend is presented across the top of the display to enable you to keep track of the effects of parameter changes you've made. Note, however, that after the 10^th run, the line color reverts to black until you clear the display.