The Resting Membrane Potential

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... 

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... 

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 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... 

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. 

A third type of K+ channel, K2F, has a structure similar to two fused Kir subunits, and only two subunits are required to form a pore (Table 6-2) [39, 40]. These channels are often called leak channels or open rectifiers because they are continuously open. Like the Kir channels they are important in setting the resting membrane potential. Their activity is often regulated by kinases. 

Resting Ca2+ influx is attributed partly to a certain level of the open probability of excitable channels, including ROCs, SOCs and VGCCs. Some SOCs may stay open due to the basal level of InsP3, while the resting membrane potential of vascular smooth muscle allows for a certain degree of activation of the Ca2+ window current (Nelson et al 1990). Additionally a non-specific influx of Ca2+, referred to as the Ca2+ leak, substantially contributes to basal influx however, its precise mechanism remains elusive (van Breemen et al 1972). 

Bolton They are not if they are at the resting membrane potential, but they are, if depolarized. 

The potential depends upon the concentration of charged ions present, the relative membrane permeability to those ions and the presence of any ionic pumps that maintain a concentration gradient. The resting membrane potential is — 60 to — 90 mV, with the cells being negatively charged inside. 

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