Plasma membrane depolarization

Specht, K.G. and Rodgers, M.A.J., Plasma membrane depolarization and calcium influx during ceU injury by photodynamic action, Biochim. Biophys. Acta, 82, 519,1993. 

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... 

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. 

In E-C coupling in the heart, the RyR2 channel releases Ca2+ from the SR on depolarization of the plasma membrane or T-tubules by CICR mechanisms. The... 

Synaptic vesicles are the organelles in axon terminals that store neurotransmitters and release them by exocytosis. There are two types, the large dense-core vesicles, diameter about 90 nm, that contain neuropeptides, and the small synaptic vesicles, diameter about 50nm, that contain non-peptide transmitters. About ten vesicles per synapse are docked to the plasma membrane and ready for release, the readily releasable pool . Many more vesicles per synapse are stored farther away from the plasma membrane, the resting pool . When needed, the latter vesicles may be recruited into the readily releasable pool. Neuronal depolarization and activation of voltage-sensitive Ca2+... 

Figure 49-8. Diagram of the relationships among the sarcolemma (plasma membrane), a T tubule, and two cisternae of the sarcoplasmic reticulum of skeletal muscle (not to scale). The T tubule extends inward from the sarcolemma. A wave of depolarization, initiated by a nerve impulse, is transmitted from the sarcolemma down the T tubule. It is then conveyed to the Ca release channel (ryanodine receptor), perhaps by interaction between it and the dihydropyridine receptor (slow Ca voltage channel), which are shown in close proximity. Release of Ca from the Ca release channel into the cytosol initiates contraction. Subsequently, Ca is pumped back into the cisternae of the sarcoplasmic reticulum by the Ca ATPase (Ca pump) and stored there, in part bound to calsequestrin.

In squid giant axons, PbTx causes a depolarization of the plasma membrane, repetitive discharges followed by depression of action potentials, and a complete blockade of excitability. This action is antagonized by TTX (83,84). PbTx depolarizes nerve terminals and induces neurotransmitter release (85,86) it depolarizes skeletal muscle cells (87) and increases the frequency of action potentials in crayfish nerve cord (88). PbTx also produces a contraction of the guinea pig ileum (89). All these effects are prevented by TTX. 

The Ca channels that have been the most extensively studied are the voltage-dependent Ca channels. These channels are usually found in plasma or transverse tubule membranes. Voltage-dependent Ca channels open in response to an appropriate membrane depolarization. Several different types of voltage-dependent Ca channels have been described and are characterized by differences in their activation and inactivation sensitivities to voltage, their kinetic properties, and their sensitivities to activation or inhibition by a variety of pharmacological agents. 

Another way to increase the entry of Ca2+ across the plasma membrane is to hyperpolarize the plasma membrane by elevating active ion transport. Fischer et al. [130] demonstrated that hyperpolarization of colonic epithelial cells (HT-29) with carbachol elevates the intracellular levels of Ca2+, [Ca2+]i while depolarization with gramicidin D or elevation of K+ in the bathing fluid reverses it. Treatment with 0.1 mM carbachol produced a spontaneous increase in [Ca2+]i from 63 nM to 901 nM. This lasted for about 3 min, beyond which a plateau level of 309 nM was maintained. While the initial Ca2+ transient was present in Ca2+-free medium containing 0.1 mM EGTA, the plateau phase was suppressed to baseline levels, suggesting that carbachol initially releases Ca2+ from the intracellular stores and subsequently increases the Ca2+ entry across the plasma membrane. In cells hyperpolarized with carbachol, induction of depolarization by ele-... 

There is considerable evidence that the release of 5-HT occurs by exocytosis, i.e. by the discharge from the cell of the entire content of individual storage vesicles. First, 5-HT is sufficiently ionized at physiological pH so that it does not cross plasma membranes by simple diffusion. Second, most intraneuronal 5-HT is contained in storage vesicles and other contents of the vesicle including SPB are released together with serotonin. By contrast, cytosolic proteins do not accompany electrical stimulation-elicited release of 5-HT. Third, the depolarization-induced release of 5-HT occurs by a calcium-dependent process indeed, it appears that the influx of extracellular calcium ions with or without membrane depolarization can increase the release of 5-HT. Calcium stimulates the fusion of vesicular membranes with the plasma membrane (see Chs 9,10). 

In regards to necrosis, it is clear that the old adage an ounce of prevention is worth a pound of cure applies. Agents that stabilize ion homeostasis have proved to be effective in preventing necrosis in cell culture studies. For example, drugs that activate plasma membrane potassium ion channels or chloride ion channels can prevent membrane depolarization and so inhibit sodium and calcium ion influx. Agents that prevent large sustained increases in intracellular free calcium levels can also prevent neuronal... 

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