Excitable cell

Ion Channels. The excitable cell maintains an asymmetric distribution across both the plasma membrane, defining the extracellular and intracellular environments, as well as the intracellular membranes which define the cellular organelles. This maintained a symmetric distribution of ions serves two principal objectives. It contributes to the generation and maintenance of a potential gradient and the subsequent generation of electrical currents following appropriate stimulation. Moreover, it permits the ions themselves to serve as cellular messengers to link membrane excitation and cellular... 

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. 

Voltage-gated Ca2+ channels are Ca2+-selective pores in the plasma membrane of electrically excitable cells, such as neurons, muscle cells, (neuro) endocrine cells, and sensory cells. They open in response to membrane depolarization (e.g., an action potential) and permit the influx of Ca2+ along its electrochemical gradient into the cytoplasm. 

Like other voltage-gated cation channels, Ca2+ channels exist in at least three states A resting state stabilized at negative potentials (such as the resting potentials of most electrically excitable cells) that is a closed state from which the channel can open. The open state is induced by depolarization. Channels do not stay open indefinitely because they are turned off during prolonged depolarization by transition into an inactivated state. Inactivation is driven both by depolarization... 

Excitability refers to the capacity of nerves and other tissues (e.g. cardiac), as well as individual cells, to generate and sometimes propagate action potentials, signals that serve to control intracellular processes, such as muscle contraction or hormone secretion, and to allow for long- and short-distance communication within the organism. Examples of excitable cells and tissues include neurons, muscle and endocrine tissues. Examples of nonexcitable cells and tissues include blood cells, most epithelial and connective tissues. 

Resting potential is a stable membrane potential in nonexcitable cells, or the most stable membrane potential between Action Potentials in excitable cells. In some excitable tissues it is impossible to define a resting potential because of continuous change in membrane potential. 

Voltage-dependent sodium channels are a family of membrane proteins that mediate rapid Na+ influx, in response to membrane depolarization to generate action potentials in excitable cells. 

The primary role of the sodium channels is to generate action potentials in excitable cells. In case of neurons, the sodium channel density is high at axon hillocks or axon initial segment where action potentials start to propagate. The sodium channels are also present in dendrites. The sodium channels contribute to amplifying synaptic inputs (particularly those distally located) and are actively involved in back propagation of action potentials into dendrites. Subtle differences in properties of sodium channels influence the dendritic processes of synaptic integration in and complex ways. 

Research in this area advanced in the 1970 s as several groups reported the isolation of potent toxins from P. brevis cell cultures (2-7). To date, the structures of at least eight active neurotoxins have been elucidated (PbTx-1 through PbTx-8) (8). Early studies of toxic fractions indicated diverse pathophysiological effects in vivo as well as in a number of nerve and muscle tissue preparations (reviewed in 9-11). The site of action of two major brevetoxins, PbTx-2 and PbTx-3, has been shown to be the voltage-sensitive sodium channel (8,12). These compounds bind to a specific receptor site on the channel complex where they cause persistent activation, increased Na flux, and subsequent depolarization of excitable cells at resting... 

All these results are clear indications that CTx and PbTx have similar modes of action and that they increase the membrane permability of excitable cells to Na ions by opening voltage-dependent Na channels. This action fully accounts for the toxicity of ciguatoxin and brevetoxins. 

Pasti L, Zonta M, Pozzan T, Vicini S, Carmignoto G (2001) Cytosolic calcium oscillations in astrocytes may regulate exocytotic release of glutamate. J Neurosci 21 477 84 Fenner R, Neher E (1988) The role of calcium in stimulus-secretion coupling in excitable and non-excitable cells. J Exp Biol 139 329-345... 

What this discussion does highlight, however, is that some modification is required to the standard dictionary definition of a neurotransmitter given in the introduction to this chapter, which sees a NT as a substance that transmits the impulse from one neuron to another neuron (or excitable cell). A more comprehensive definition of a NT might be... 

In previous reviews on this matter by Gogelein [9] and myself [10] it has been pointed out that the Cl -channels of the central nervous system and of skeletal muscle are distinct from those of non-excitable cells. The latter entity is in itself obviously heterogeneous with respect to its occurrence and function. In apolar as well as in polarized cells Cl -channels may be involved in volume regulation. As a simple rule gating of K" - and Cl -channels is likely to occur whenever cell volume has to be down-regulated [11], as is the case in regulatory volume decrease of cell volume. A simple means to induce this phenomena is the exposure of cells to hypoosmolar solutions [12]. For example Cl -channels play an important role in... 

In many epithelia Cl is transported transcellularly. Cl is taken up by secondary or tertiary active processes such as Na 2Cl K -cotransport, Na Cl -cotransport, HCOJ-Cl -exchange and other systems across one cell membrane and leaves the epithelial cell across the other membrane via Cl -channels. The driving force for Cl -exit is provided by the Cl -uptake mechanism. The Cl -activity, unlike that in excitable cells, is clearly above the Nernst potential [15,16], and the driving force for Cl -exit amounts to some 2(f-40mV. 

In the following the Cl -channels will be subdivided into those of the central nervous system, of muscle and Torpedo electroplax, of apolar non-excitable cells and of epithelia. 

Cl -channels with large, intermediate, and small conductance have been found in apolar non-excitable cells. In macrophages and in fibroblasts large Cl -channels were found [33,44]. The latter preparation, lymphocytes, monocytes and keratino-cytes also contain an intermediate conductance outwardly rectifying Cl -channel... 

If a substance that can form a transmembrane channel exists in several conformations with different dipole moments, and only one of these forms is permeable for ions, then this form can be favoured by applying an electric potential difference across the membrane. The conductivity of the membrane then suddenly increases. Such a dependence of the conductivity of the membrane on the membrane potential is characteristic for the membranes of excitable cells. 

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... 

Le Novere, N., Changeux, J.P. Molecular evolution of the nicotinic acetylcholine receptor an example of multigene family in excitable cells. J. Mol. Evol. 40 155, 1995. 

Neuron The electrically excitable cell of the nervous system. 

Ionized calcium (Ca2+) is the most common signal transduction element in cells [66], Excitable cells, like neurons, contain voltage-dependent Ca2+ channels, which enable these cells to drastically increase cytosolic calcium levels. Rapid fluctuations in presynaptic... 

MEMBRANE POTENTIALS AND ELECTRICAL SIGNALS IN EXCITABLE CELLS 95... 

Excitable cells have a negative membrane potential 95 Real cells are not at equilibrium 97... 

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