Resting Membrane Potential -
All cells have a potential difference across their plasma membrane. It is referred to as a potential difference because the potential inside of the cell is measured with respect to the potential of the solution bathing the cell. This potential difference is referred to as the membrane potential (Vm)
. The resting membrane potential (Vrest)
refers to a situation in which the cell is at rest and no perturbations have been done to change the potential. Therefore, Vm
can be used to refer to the membrane potential in general, and Vrest
can be used to refer to the resting membrane potential (i.e., Vm
when the cell is at rest). In most cells examined, the resting membrane potential is inside negative (i.e., inside of the cell is negative with respect to the outside, which serves as the reference). In most mammalian cells, the resting membrane potential is around −50 mV (−0.05 V). The value of the resting membrane potential varies from cell to cell, and ranges from about −20 mV to −100 mV. For example, in a typical neuron, its value is −70 mV, in a typical skeletal muscle cell, its value is −90 mV, and in a typical epithelial cell, its value is closer to −50 mV. The symbol V
is normally used to refer to the membrane potential (because the Volt
is the SI unit for voltage), and because the values are small, they are commonly reported in mV (millivolts; 1 V = 1000 mV). The goals of this lecture are (1) to understand how
the membrane potential is established and (2) the factors that govern the value of the membrane potential.
In non-excitable cells
, such as epithelial cells and adipose cells (and others), the resting membrane potential does not change appreciably over time. Therefore, Vm
at all times. In excitable cells
(such as neurons, muscle cells, and some endocrine cells), however, upon stimulation of the cell, the membrane potential can change dramatically for short periods of time (milliseconds to hundreds of milliseconds). Therefore, in excitable cells the membrane potential is not always at the resting membrane potential. As we will see later, deviations from the resting membrane potential in excitable cells are extremely important to the physiological function of these cells. In neurons, rapid changes in the membrane potential bring about the nervous impulse
(see lecture on Neuronal Action Potential
), which is the basis of neuronal signaling. In muscle cells, changes in the membrane potential bring about contraction. In endocrine cells, changes in the membrane potential bring about hormone secretion.
Figure 1. Measurement of the membrane potential.
The membrane potential can be measured by using a special voltmeter that is electrically connected to the interior of the cell via a glass microelectrode. The glass electrode is typically filled with an electrolyte solution such as 3 M KCl, which allows for electrical continuity between the cell interior and the wire connected to the voltmeter. While beyond, the scope of this lecture, the electrode in the glass micropipette as well as the reference (i.e., bath) electrode are silver/silver chloride (Ag/AgCl) electrodes, which allow for electrical continuity between the electrolyte solutions (inside the glass micropipette and bathing solution of the cell) and the wires that connect to different leads of the voltmeter. Because the magnitude of the membrane potential is very small, the voltmeter must also amplify the signal for proper measurement.
The membrane potential can be measured by using glass microelectrodes and a special voltmeter (Fig. 1). Glass micropipettes are prepared by heating the center of a glass capillary tube until it becomes soft, and pulling the two ends apart such that the center of the tube tapers to a very fine point and finally breaks (resulting in two glass micropipettes each with a fine tip). Modern microelectrode pullers have been designed that can accurately and reproducibly produce tapered glass tips of desired dimensions appropriate for cells of different sizes. The tip of the glass microelectrode is very small (∼1 μm in diameter) and does not "kill" the cell. The glass micropipettes are then filled with an appropriate electrolyte solution. In addition, a Ag/AgCl (silver/silver chloride) wire is placed inside the micropipette such that electrical continuity may be established between the electrolyte solution and the voltmeter. At this point, the glass micropipettes can be referred to as glass microelectrodes and may be used to impale the cell (i.e., penetrate the cell plasma membrane) and properly connected to one lead of an amplifier. A reference electrode is also placed in the physiological buffer bathing the impaled cell and is electrically connected to the other lead of the amplifier. This configuration can now be used to measure the potential difference between the outside and inside of the cell (i.e., across the plasma membrane). By convention, the potential of the extracellular fluid is considered to be the reference or zero value. Therefore, the intracellular potential is always measured with respect to the extracellular (or reference) potential. Equation 1 describes the value of the membrane potential given that the extracellular potential is the reference value of zero.
where Vi and Vo refer to the inside and outside potential values, respectively.
Other experimental tools can also be used to measure the membrane potential. One approach that has been gaining in popularity is the use of voltage-sensitive fluorescent dyes. However, microelectrode methods remain the method of choice for measuring the membrane potential.
Figure 2. Depolarization, repolarization, and hyperpolarization.
Using the resting membrane potential as the reference point, a change in the membrane potential in the positive direction (i.e., more positive than the resting potential) is called depolarization. After a depolarization, return to the resting membrane potential is call repolarization. Using the resting membrane potential as the reference point, a change in the membrane potential in the negative direction (i.e., more negative than the resting potential) is called hyperpolarization.
As mentioned above, the membrane potential is negative; i.e., inside negative with respect to the outside. Thus, it can be said that there is asymmetry with respect to the value of the membrane potential across the plasma membrane. Because of this asymmetry in charge distribution, the membrane is considered to be polarized. If the membrane potential becomes less negative (or more positive) than the resting value, the change is referred to as depolarization (Fig. 2). Repolarization refers to the return of the membrane potential toward the normal resting value after a depolarization. Conversely, if the membrane potential becomes more negative than the resting value, the change is referred to as hyperpolarization.
It is important to keep in mind that the potential difference occurs at the level of the cell plasma membrane. This is because biological membranes can act in a similar way as capacitors (Fig. 3). A capacitor is simply a device that allows separation of electrical charge, thereby allowing for the establishment of an electric field (i.e., voltage) across the plates of the capacitor. Typical capacitors used in electrical circuits are made up of two metal plates closely apposed to one another, but are separated by a non-conducting medium (such as air, vacuum, or other material). Because of the close proximity of the plates, an electric field can be established between the two plates. Biological membranes are similar to capacitors because they separate solutions in two conductive compartments by the very short-distance, non-conductive, hydrophobic core of the membrane (∼3 nm). Charge separation across the membrane leads to an electric field across the membrane. This electric field gives rise to the measured membrane potential.
Figure 3. The membrane potential is similar to a voltage difference across the plates of a capacitor.
In the absence of integral membrane proteins, biological membranes have similar electrical properties to those exhibited by parallel-plate capacitors. Both parallel-plate capacitors (A) and biological membranes (B) are made up of a non-conductive medium that separates two conductive media. In the case of a parallel-plate capacitor, the non-conductive medium is air or vacuum that separates the conductive parallel plates. In the case of a biological membrane, the non-conductive medium is the hydrophobic core of the membrane, where the fatty acid tails of phospholipid molecules reside. The hydrophobic membrane core (∼3 nm) separates the conductive extracellular and intracellular electrolyte solutions. Thus, the lipid bilayer can separate charge (Q) between the extracellular and intracellular conductive media and this charge separation brings about an electrical potential difference across the bilayer (referred to as the membrane potential, Vm).
Our goals in this lecture are to understand (1) how the membrane potential is established, and (2) the factors that govern the value (e.g., −70 versus −90 mV) of the membrane potential, and finally (3) how the membrane potential is maintained.
Posted: Saturday, February 15, 2014