Plasmalemmal Ca

Regulation of the Plasmalemmal Ca + Pump by Cyclic Nucleotide-Dependent Protein Kinases... 

Fig. 2. Schematic diagram for the activation of smooth muscle through phosphorylation of regulatory light chains of myosin. Upon activation of smooth muscle by membrane depolarisation or activation of a receptor (R) through an agonist (L) the cytosolic Ca " increases due to an influx of Ca through plasmalemmal Ca channels or IP3 mediated release from the sarcoplasmic reticulum (SR). Ca binds to calmodulin (CaM) and activates the myosin light chain kinase (MLCK). Myosin is dephosphorylated by specific phosphatase(s) (MLCP).

The movement of Ca against its energy gradient to establish the concentration gradient is thermodynamically paid for by coupling to the bond energy of the terminal phosphate of ATP, as is true in so many other cases. The stoichiometry of the plasmalemmal piunp reaction is not agreed upon. Therefore, we write simply ... 

The path of entry of extracellular Ca " during the sustained phase of contraction in ASM has eluded definition in the absence, to date, of the demonstration of physiologically relevant VDCs or ROCs. These data raise the possibility that following agonist activation, when the buffering capacity of the sr is abolished, the passive plasmalemmal leak can provide sufficient extracellular Ca " to sustain the onist-induced, or receptor-mediated (Murray and Kotlikoflf, 1991), plateau rise in cytosolic Ca which accompanies maintained contraction. 

The sr has been identified as the major intracellular source of activator Ca " in both smooth and striated muscle (Somlyo etal., 1981 Bond etcd., 1984 Somlyo, 1985). The sr of smooth muscle is a system of membranous tubules which has components closely underlying the surface plasmalemmal membrane, as well as deeper portions contiguous with the double membrane of the... 

In addition to this function of controlling the overall cytosolic Ca " concentration adjacent to the myofilaments in the deep cytosol, there is evidence that the st also plays a role in controlling the influx of extracellular Ca -" through the plasmalemmal membrane. This has led to the independent proposal of two concepts - the superficial buffer barrier hypothesis and the capacita-tive model - both of which attempt to link sr function to extracellular Ca " influx. 

Alternatively, hyperpolarization, induced by channel opening, may prevent the maintenance of contraction by an effea on Ca handling by the intracellular Ca " stores in ASM (Chopra etal., 1992). Sarcoplasmic reticulum membranes contain selective channels. These channels facilitate the flux of K into the sr from a pool of high concentration in the cytosol (Coronado et al., 1980). Although the predominant mode of action of channel openers is assumed to occur by hyperpolarization of the plasmalemmal... 

It should be clear that in comparison to the present knowledge on Na -K+ ATPase, the current understanding of Ca transport is sparse. The relative importance of plasmalemmal, mitochondrial, and reticular systems in the overall regulation and control of free cytoplasmic Ca remains to be elucidated and is obviously a fruitful area of research for the future. 

It is striking that in aU of these O2-sensitive tissues, the effectors appear to be K+ channels (Fig. 2). Isolated PASMCs, ADMCs (or the pheochromocytoma cells, PC 12, used as models for ADMCs), and cells from the CB and NEB respond to hypoxia with a decrease in the outward K+ current (Fig. 2). This results in depolarization of the plasmalemmal membrane, increased opening of voltage-gated Ca + channels, influx of Ca +, and an increase in [Ca +] . In the case of PASMC, this results in the activation of actin-myosin and contraction. In CB glomus cells, it results in release of dopamine from vesicles and increased neural transmission to the brainstem via the IX cranial nerve. Similarly, in ADM and NEB cells K+ current inhibition, membrane depolarization, and increases in [Ca +] cause the release of... 

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