Membrane potential hyperpolarization

Nelson I would like to return to what David Eisner mentioned about the plasma membrane determining the steady-state free Ca2+, and what Rick Paul said about sparks and long-conductance Ca2+-dependent K+ (BK) channels. We have looked at cerebral arteries from PLB knockout mice. The spark frequency and the associated transient BK current frequency are elevated by about a factor of three. SR load goes up, the membrane potential hyperpolarizes and the artery relaxes. It would be useful to measure membrane potential under all the conditions as well as determine the voltage dependence of tone, to make sure that your manipulations are not simply changing the membrane potential. 

Zeng, Y., Clark, E.N., and Florman, H.M. (1995). Sperm membrane potential Hyperpolarization during capacitation regulates zona pellucida dependent acrosomal secretion. Dev. Biol. 777 554-,563. 

Certain synthetic potassium channel openers have been shown to activate K a channels, such as NS-004 (Sargenteta/., 1993)andNS-1619. However, iberiotoxin was unable to reverse the functional effects of NS-004, and therefore its mechanism of action may also involve inhibition of calcium current rather than activation of K a channels. Some drugs (e.g., cro-makalim) that activate K -p channels have also been shown to activate K channels in aortic smooth muscle cells but not in other types of arterial smooth muscle. Since blockers of K a channels (charybdotoxin and <1 mM TEA+) had no effect on membrane potential hyperpolarizations or dilations to any of... 

In the following, the cardiac action potential is explained (Fig. 1) An action potential is initiated by depolarization of the plasma membrane due to the pacemaker current (If) (carried by K+ and Na+, which can be modulated by acetylcholine and by adenosine) modulated by effects of sympathetic innervation and (3-adrenergic activation of Ca2+-influx as well as by acetylcholine- or adenosine-dependent K+-channels [in sinus nodal and atrioventricular nodal cells] or to dqjolarization of the neighbouring cell. Depolarization opens the fast Na+ channel resulting in a fast depolarization (phase 0 ofthe action potential). These channels then inactivate and can only be activated if the membrane is hyperpolarized... 

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). 

Depolarization occurs when the membrane potential becomes less negative, moving toward zero. As will be discussed, depolarization makes the neuron more excitable. Hyperpolarization occurs when the membrane potential becomes more negative, moving away from zero. Hyperpolarization tends to make the neuron less excitable. Depolarization and hyperpolarization signals are transient or short-lived. Once the stimulus has been removed, the membrane potential returns to its resting state. Following... 

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.

Parasympathetic stimulation causes a decrease in heart rate. Acetylcholine, which stimulates muscarinic receptors, increases the permeability to potassium. Enhanced K+ ion efflux has a twofold effect. First, the cells become hyperpolarized and therefore the membrane potential is farther away from threshold. Second, the rate of pacemaker depolarization is decreased because the outward movement of K+ ions opposes the effect of the inward movement of Na+ and Ca++ ions. The result of these two effects of potassium efflux is that it takes longer for the SA node to reach threshold and generate an action potential. If the heart beat is generated more slowly, then fewer beats per minute are elicited. 

Recent work using confocal microscopy has found localized increases of [Ca2+]j named Ca2+ sparks which are due to the release of Ca2+ from one or a small number of RyRs (Jaggar et al 2000). These localized releases of Ca2+ activate Ca2+-dependent channels in the surface membrane (Perez et al 2001). Activation of the Ca2+-activated K+ current will hyperpolarize the membrane potential (Herrera et al 2001) and thereby decrease Ca2+ entry into the cell on voltage-dependent Ca2+ channels. This provides a mechanism whereby Ca2+ release from the SR can decrease contraction. It is therefore important, in different smooth muscles, to consider to what extent SR Ca2+ release activates rather than decreases contraction. It is, of course, possible that, in the same smooth muscle, SR release may sometimes directly activate contraction and, at other times, decrease it by activating K+ channels. 

An interesting idea is that in small arteries such as the rat basilar STOCs elicited by sparks can exert a negative feedback on the membrane potential of the smooth muscle syncytium (cells are linked by low resistance pathways) the hyperpolarization so produced will reduce Ca2+ entry through voltage-dependent Ca2+ channels. Thus, in pressurized arteries where the membrane potential is lower than in the relaxed state and there is significant Ca2+ influx into... 

Nelson Carbachol-induced constrictions are nicely relaxed by membrane hyperpolarization. I would say that measuring the membrane potential under... 

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