Influx of Extracellular Calcium

The free Ca concentration in the extracellular fluid surrounding airway smooth muscle is approximately 1.5 mM, while cytosolic Ca is below the micromolar range. The large electrochemical gradient across the plas-malemmal membrane results in a continuous passive leak of Ca into the cytosol. This leak of Ca into the cytosol is normally compensated for by the active Ca removal mechanisms (discussed later) which return Ca to the extracellular space, thereby preventing a rise in the cytosolic Ca concentration. 

In addition to this passive leak, extracellular Ca may gain access to the cytosol by passing through ion channels in the cell membrane (Fig. 9.3). As for other smooth muscle, two types of Ca channel have been proposed 

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PBAN binding to a receptor results in signal transduction events to stimulate the pheromone biosynthetic pathway (Fig. 5). Receptor activation results in the influx of extracellular calcium and has been demonstrated in a number of moths [163-168]. The increase in cytosolic calcium can directly stimulate pheromone biosynthesis in some moths [165-168] or it will stimulate the production of cAMP [169,170]. So far cAMP has only been implicated in signal... 

Fig. 5 Proposed signal transduction mechanisms that stimulate the pheromone biosynthetic pathway in Helicoverpa zea and Bombyx mori. It is proposed that PBAN binds to a G protein-coupled receptor present in the cell membrane that upon PBAN binding will induce a receptor-activated calcium channel to open causing an influx of extracellular calcium. This calcium binds to calmodulin and in the case of B. mori will directly stimulate a phosphatase that will dephosphorylate and activate a reductase in the biosynthetic pathway. In H. zea the calcium-calmodulin will activate adenylate cyclase to produce cAMP that will then act through kinases and/or phosphatases to stimulate acetyl-CoA carboxylase in the biosynthetic pathway...

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). 

Muitfay M, Rao GH, Robinson P, and Reddy R. (1995). Influx of extracellular calcium and agonist-coupling appear essoitial for the activation of thromboxane AfdepeadeiA phos dK>lipase A human platelets. Prostaglandin Leuk. Essen. Fatty Acids. 53,31-39. 

IP.1 is also converted to inositol l.3.4..5-tetrakisphosphate (IP4). IP.) also ads as an intracellular messenger, resulting in an influx of extracellular calcium. IP4 is converted to IP.d 1.3.4). which Is Jepho.sphorylaled stepwise to imwilul 1.4-diphosphate, inositol I-phosphate, then ino.sitol. The inositol is then incorporated into DAG to form pho.sphatidylinositol (PI). PI is sequentially phosphorylatcd to formphos-phatidylino.sitol 4-phosphatc (PIP) and PIP-. 

Thomas, P. and Meizel, S. (1988). An influx of extracellular calcium is required for initiation of the human sperm acrosome reaction induced by human follicular fluid. Gamete Res. 20 397-411. 

Digitalis glycosides cause an influx of extracellular calcium and an accumulation of extracellular potassium. The increased levels of extracellular potassium decrease the rate of repolarization of the cardiac cell. Thus, as levels of the drug approach the toxic range, accumulated extracellular potassium causes a lengthening of phase 3 of the cardiac action potential and an increase in the length of time between depolarizations. Thus, bradycardia is seen. 

Agents that increase intracellular calcium, causing an influx of extracellular calcium following receptor activation or the release of calcium from intracellular stores, cause endothelium- (and NO-) dependent relaxation in... 

Fig. 15 Intracellular phosphatidyl inositol metabolism and postulated roles for inositol phosphates as secondary messengers (adapted from Housley, 1987). (1) One or more of the inositol phosphates (including I(1,4,5)P3) stimulates rapid release of calcium from intracellular stores. (2) Feedback from initial rapid calcium release stimulates intracellular inositol phosphate metabolism. (3) Secondary increase in intracellular calcium levels through activation of membrane calcium-gates and influx of extracellular calcium stimulated by inositol phosphates. PC = phospholipase C.

Endothelin-1 (ET-1) is a 21-amino-acid peptide that is produced by the vascular endothelium. It is a very potent vasoconstrictor that binds to VSM endothelin receptors ETa and ETB(Fig. 29.1). The ET-1 receptors are linked to the Gq protein and IP3 signal transduction pathway (Fig. 29.11). Therefore, ET-1 causes sarcoplasmic reticulum release of calcium, increasing the VSM contractility. Vascular endothelial cells secrete the majority of ET-1. The endothelins bind to two receptor subtypes ETa, and ETb. Invasculartissue, ETa is located predominantly on smooth muscle cells, whereas ETb is found on both endothelial and smooth muscle cells. Activation of ETa by ET-1 leads to potent vasoconstriction from an increase in cytosolic calcium levels via influx of extracellular calcium and release from intracellular stores (Fig. 29.1). The actions of ETb are more complicated. Like ETa, ET-1 activation of ETb on VSM cells leads to vasoconstriction. Furthermore, some studies suggest that in the pulmonary hypertensive state, blockade of both ETa and ETb is necessary to achieve maximal vasodilation. Activation of ET-B by ... 

The acidification produced by palytoxin was due to an influx of extracellular calcium, since it was completely abolished in a calcium-free medium. In addition, toxin-induced intracellular acidification was completely prevented by several inhibitors of the plasma membrane calcium ATPase,... 

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