Membrane potential resting

For many years, it has been known that many individual biological cells maintain different distributions in ionic concentrations and an electrical potential difference between their intracellular and extracellular phases at the resting state (Table 19). In some cells, upon application of an appropriate stimulus (electrical depolarization or chemical stimulus), the cells exhibit a time-dependent response via a potential difference across the cell membranes which does not necessarily follow Ohm s law. The former potential is called a resting membrane potential and the latter an excitation potential. We would like to review the origins of these electrical potential differences across the cell membrane. 

Potential due to Ionic Distribution or Movement across Membranes 

In order to explain this transmembrane potential, a number of authors have proposed membrane potential theories. Historically, the first membrane potential theory for biological systems was the use of the concept of the Donnan membrane equilibrium. 

When ionic molecules are in an aqueous solution, the ion has electrochemical potential 

Ion Distributions, Relative Ionic Permeabilities, and Resting Potential of Various Cells 

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Automa-ticity. Special cardiac cells, such as SA and AV nodal cells, His-bundle cells, and Purkinje fibers, spontaneously generate an impulse. This is the property of automaticity. Ectopic sites can act as pacemakers if the rate of phase 4 depolarization or resting membrane potential is increased, or the threshold for excitation is reduced. 

The resting membrane potential of most excitable cells is around —60 to —80 mV. This gradient is maintained by the activity of various ion channels. When the potassium channels of the cell open, potassium efflux occurs and hyperpolari2ation results. This decreases calcium channel openings, which ia turn preveats the influx of calcium iato the cell lea ding to a decrease ia iatraceUular calcium ia the smooth muscles of the vasculature. The vascular smooth muscles thea relax and the systemic blood pressure faUs. 

Traditionally concepts of ion selective permeation of biological membranes have centered on differences in the effective radii of hydrated nuclei. An example of that perspective derives from consideration of the resting membrane potential, E, which in the squid axon is approximated by the Nernst equation... 

The M-channels (M for muscarine) are expressed in the peripheral sympathetic neurons and CNS. In the absence of acetylcholine, the M-channel opens at resting membrane potential and dampens neuronal responsiveness to synaptic inputs. Acetylcholine inhibits M-channel activity by activation of Ml receptor. 

The GABAA-receptor and the glycine receptor are Cl-channels (Table 1). When they open at a resting membrane potential of about -60 mV, the consequence is an entry of Cl-, hyperpolarization and an inhibitory postsynaptic potential (DPSP Fig. 1). 

Figure 1.4 Ionic basis for excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs). Resting membrane potential ( — 70 mV) is maintained by Na+ influx and K+ efflux. Varying degrees of depolarisation, shown by different sized EPSPs (a and b), are caused by increasing influx of Na. When the membrane potential moves towards threshold potential (60-65 mV) an action potential is initiated (c). The IPSPs (a b ) are produced by an influx of Cl. Coincidence of an EPSP (b) and IPSP (a ) reduces the size of the EPSP (d)...

Figure 11.5 Chloride distribution and the GABAa response. The change in membrane voltage (Fm) that results from an increase in chloride conductance following activation of GABAa receptors is determined by the resting membrane potential and the chloride equilibrium potential (Fci)- (a) Immature neurons accumulate CF via NKCC, while mature neurons possess a Cl -extruding transporter (KCC2). (b) In immature neurons GABAa receptor activation leads to CF exit and membrane depolarisation while in mature neurons the principal response is CF entry and h5q)erpolarisation. This is the classic inhibitory postsynaptic potential (IPSP)...

ATP certainly fulfils the criteria for a NT. It is mostly synthesised by mitochondrial oxidative phosphorylation using glucose taken up by the nerve terminal. Much of that ATP is, of course, required to help maintain Na+/K+ ATPase activity and the resting membrane potential as well as a Ca +ATPase, protein kinases and the vesicular binding and release of various NTs. But that leaves some for release as a NT. This has been shown in many peripheral tissues and organs with sympathetic and parasympathetic innervation as well as in brain slices, synaptosomes and from in vivo studies with microdialysis and the cortical cup. There is also evidence that in sympathetically innervated tissue some extracellular ATP originates from the activated postsynaptic cell. While most of the released ATP comes from vesicles containing other NTs, some... 

The ventricular action potential is depicted in Fig. 6-2.2 Myocyte resting membrane potential is usually -70 to -90 mV, due to the action of the sodium-potassium adenosine triphosphatase (ATPase) pump, which maintains relatively high extracellular sodium concentrations and relatively low extracellular potassium concentrations. During each action potential cycle, the potential of the membrane increases to a threshold potential, usually -60 to -80 mV. When the membrane potential reaches this threshold, the fast sodium channels open, allowing sodium ions to rapidly enter the cell. This rapid influx of positive ions... 

Describe how the resting membrane potential is developed and maintained... 

Describe how differences in ion distribution and permeability contribute to the resting membrane potential... 

The Na+-K+ pump also plays a vital role in this process. For each molecule of ATP expended, three Na+ ions are pumped out of the cell into the ECF and two K+ ions are pumped into the cell into the ICF. The result is the unequal transport of positively charged ions across the membrane such that the outside of the cell becomes more positive compared to its inside in other words, the inside of the cell is more negative compared to the outside. Therefore, the activity of the pump makes a small direct contribution to generation of the resting membrane potential. 

The other, even more important effect of the Na+-K+ pump is that it maintains the concentration differences for sodium and potassium by accumulating Na+ ions outside the cell and K+ ions inside the cell. As previously discussed, the passive diffusion of these ions down their concentration gradients is predominantly responsible for generating the resting membrane potential. Sodium diffuses inward and potassium diffuses outward. The continuous activity of the pump returns the Na+ ions to the ECF and the K+ ions to the ICF. Therefore, it can be said that the pump also makes an indirect contribution to generation of the resting membrane potential. 

Figure 4.1 Types of changes in membrane potential. The resting membrane potential in a typical neuron is -70 mV. Movement of the membrane potential toward zero (less negative) is referred to as depolarization. The return of the membrane potential to its resting value is referred to as repolarization. Movement of the membrane potential further away from zero (more negative) is referred to as hyperpolarization.

The ability to depolarize spontaneously is related to the unstable resting membrane potentials in single-unit smooth muscle. Two types of spontaneous depolarizations may occur ... 

The sinoatrial (SA) node is located in the wall of the right atrium near the entrance of the superior vena cava. The specialized cells of the SA node spontaneously depolarize to threshold and generate 70 to 75 heart beats/ min. The "resting" membrane potential, or pacemaker potential, is different from that of neurons, which were discussed in Chapter 3 (Membrane Potential). First of all, this potential is approximately -55 mV, which is less negative than that found in neurons (-70 mV see Figure 13.2, panel A). Second, pacemaker potential is unstable and slowly depolarizes toward threshold (phase 4). Two important ion currents contribute to this slow depolarization. These cells are inherently leaky to sodium. The resulting influx of Na+ ions occurs through channels that differ from the fast Na+ channels that cause rapid depolarization in other types of excitable cells. Toward the end of phase... 

However, in the SAnode, the action potential develops more slowly because the fast Na+ channels do not play a role. Whenever the membrane potential is less negative than -60 mV for more than a few milliseconds, these channels become inactivated. With a resting membrane potential of -55 mV, this is clearly the case in the SA node. Instead, when the membrane potential reaches threshold in this tissue, many slow Ca++ channels open, resulting in the depolarization phase of the action potential. The slope of this depolarization is less steep than that of neurons. 

The action potential generated in the ventricular muscle is very different from that originating in the SA node. The resting membrane potential is not only stable it is much more negative than that of the SA node. Second, the slope of the depolarization phase of the action potential is much steeper. Finally, there is a lengthy plateau phase of the action potential in which the muscle cells remain depolarized for approximately 300 msec. The physiological significance of this sustained depolarization is that it leads to sustained contraction (also about 300 msec), which facilitates ejection of blood. These disparities in the action potentials are explained by differences in ion channel activity in ventricular muscle compared to the SA node. 

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