Receptor operated channels

Another mechanism in initiating the contraction is agonist-induced contraction. It results from the hydrolysis of membrane phosphatidylinositol and the formation of inositol triphosphate (IP3)- IP3 in turn triggers the release of intracellular calcium from the sarcoplasmic reticulum and the influx of more extracellular calcium. The third mechanism in triggering the smooth muscle contraction is the increase of calcium influx through the receptor-operated channels. The increased cytosolic calcium enhances the binding to the protein, calmodulin [73298-54-1]. 

Postjunctional aj-adrenoceptors are always found in veins, arteries, and arterioles. Activation of these receptors results in the entry of extracellular calcium through receptor-operated channels and in the release of intra-cellularly stored calcium this is brought about through the participation of the inositol triphosphate second-... 

Cellular calcium regulation. Depicted are several sites that control calcium entry, efflux, and sequestration. 1. Na+, Ca++ exchange. 2. Receptor-operated channels. 3. Voltagegated channels. 4. Leak pathways. 5, 6. Entry and efflux in sarcoplasmic reticulum. 7. Plasma membrane pump. 

Less well-defined but particularly important in terms of the function of non-neuronal cells are so-called receptor-operated channels [6,7]. By definition these are channels in the plasma membrane which open in response to hormone-receptor interaction without a change in membrane potential. The mechanism of their opening may either be by a direct coupling of receptor (possibly via a G protein) with the channel, or by an indirect coupling via the generation of an intracellular messenger such as cAMP or the putative messenger, inositol 1,3,4,5-tetrakisphosphate. 

The flux of Ca2+ through the ACTH receptor-operated channel leads to the CaM-dependent activation of adenylate cyclase. Hence, either a low concentration of ACTH and/or an increase in K+ concentration leads both to an influx of Ca2+ through this channel and to the activation of adenylate cyclase. Higher concentrations of ACTH acting via a second type of receptor activate adenylate cyclase via the classic Gs protein mechanism. These two ACTH-dependent inputs activate adenylate cyclase in a synergistic fashion. 

The flux of Ca2+ through the AII- receptor-operated channel is increased only when PIP2 turnover is stimulated and C-kinase activated. An increase in flux through this channel leads to a stimulation of C-kinase activity but not to a stimulation of adenylate cyclase. 

The net effect of dopamine is thus likely to depend on the degree of activation of D1 and D2 receptors, on the contribution of NMDA and AMPA receptor-operated channels to the synaptic response, and the interplay between VSCCs and synaptic responses. Generally, the D2 effect predominates, i.e. dopamine inhibits depolarization and firing evoked by glutamate (Cepeda et al., 1992, 1993). 

The immediate short-term effects of dopamine are mediated by voltage and receptor-operated channels. The effects depend on the membrane potential of the postsynaptic cell, and its recent history, because these variables determine the state of the channels modulated by dopamine. At hyperpolarized potentials, rapidly inactivating channels are available, and modulating them can have effects on the transition from hyperpolarized Down states to depolarized Up states. After prolonged periods in the depolarized states, these channels are inactivated. If a dopamine pulse occurs at this time the effects on noninactivating channels will predominate. 

Cyclic GMP decreases basal and stimulated concentrations of intracellular Ca (Nakashima et al, 1986 Johansson and Haynes, 1992). A number of Ca handling systems have been identified in platelets including receptor operated channels, passive leak, Ca -ATPase extrusion pump, the NaV Ca exchanger, Ca -accumulating ATPase pump of the dense tubular membrane (an intraplatelet membrane Ca store) and passive leakage and receptor operated Ca chatinels in the dense tubular membrane. In principle, all these... 

Ca + mobilized in response to membrane stimuli is derived from either intra- or extracellular sources (Figure 2). Membrane Ca + channels mediating Ca2+ entry have been classified into two major types (18-20). Receptor-operated channels (ROC, Figure 2) are associated with membrane receptors and are activated by specific agonist-receptor interactions, whilst potential-dependent channels (PDC, Figure 2) are activated by membrane depolariza-... 

One would expect membrane hyperpolarization by any mechanism to be in- or less effective in reducing Ca influx via receptor-operated than voltage-dependent channels but this does not appear to have been systematically studied. Whether receptor-operated channels are inactivated with time or closed by any other mechanism than removal of the occupying agonist, is unclear. 

In those secretory tissues where extracellular calcium is necessary for secretion, calcium enters by way of plasma membrane channels. Therefore, the nature of membrane channels is obviously very important. Are the channels uniform on a given cell Do their characteristics vary from tissue to tissue Many questions remain unanswered, but several studies suggest that a cell may have more than one type of calcium channel. Although not a secretory tissue, smooth muscle has two types of calcium channel potential sensitive channels and receptor operated channels (30). So, in this tissue [and probably in secretory tissues as well (31)], the nature of the stimulus may determine which channels are opened, the extent of calcium entry and the extent of the response. A high potassium solution, which is commonly used to activate calcium mediated responses, would open potential dependent channels whereas drugs acting on their respective receptors would open a different set of channels, but cause the same overall response. 

Under normal conditions, the extraceUnlar concentration of calcium is in the milhmolar range (l(h M), whereas its intracellular concentration is less than l(h M. The cytoplasmic concentration of calcium is increased through the actions of receptor-operated channels, voltage-activated channels, or ionic pumps. In addition, calcium can be released from internal stores (see also Figure 103). 

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