Junctional stores

Blaustein With regard to the stores releasing Ca2+, here you are talking about indirect functional observations when you study the releasable pool. If we actually look at the store itself with furaptra and use high concentrations of an agonist or maximal doses of caffeine, it releases some Ca2+, but the Ca2+ doesn t go down much below 50/tM. You can release more if you use the Ca2+-free solution or ionomycin. The SR is not really empty. Our feeling is that there are multiple stores. There may be some stores that can be depleted relatively easily, whereas other stores are more difficult to deplete. I have some evidence that the junctional stores may be the ones that you are talking about release of Ca2+ is probably not complete . 

The MOSEET has three regions of operation. The cutoff region occurs for V g < Up. In this region, the drain-to-source current is the reverse saturation current of the back-to-back source and drain junctions. This leakage current is small but nonzero and allows charge to leak off capacitors which are isolated by cutoff MOSFETs. Because this is how bits are stored in dynamic memory (DRAM) ceUs, DRAMs must be regularly refreshed to retain their memory. 

The commercial units have a very low thermal capacity and very high response speeds. Some are available with several independent channels and a common cold junction. Each channel is scanned in turn by the instrument, and the readings either displayed or stored for future recovery. Accuracies of better than 0.2 per cent are possible. Thermocouples are available to cover a very wide range of temperatures, their cost is low and they have a small mass, so minimizing the intrusive effect on the surface at the point where the temperature is being measured. The output characteristics (output voltage versus temperature) are reasonably linear but the measurement accuracy is not particularly high. 

Purinergic System. Figure 2 Schematic of sympathetic cotransmission. ATP and NA released from small granular vesicles (SGV) act on P2X and a-i receptors on smooth muscle, respectively. ATP acting on inotropic P2X receptors evokes excitatory junction potentials (EJPs), increase in intracellular calcium ([Ca2+]j) and fast contraction while occupation of metabotropic ar-adrenoceptors leads to production of inositol triphosphate (IP3), increase in [Ca2+]j and slow contraction. Neuropeptide Y (NPY) stored in large granular vesicles (LGV) acts after release both as a prejunctional inhibitory modulator of release of ATP and NA and as a postjunctional modulatory potentiator of the actions of ATP and NA. Soluble nucleotidases are released from nerve varicosities, and are also present as ectonucleotidases. (Reproduced from Burnstock G (2007) Neurotransmission, neuromodulation cotransmission. In Squire LR (ed) New encyclopaedia of neuroscience. Elsevier, The Netherlands (In Press), with permission from Elsevier). 

To achieve their different effects NTs are not only released from different neurons to act on different receptors but their biochemistry is different. While the mechanism of their release may be similar (Chapter 4) their turnover varies. Most NTs are synthesised from precursors in the axon terminals, stored in vesicles and released by arriving action potentials. Some are subsequently broken down extracellularly, e.g. acetylcholine by cholinesterase, but many, like the amino acids, are taken back into the nerve where they are incorporated into biochemical pathways that may modify their structure initially but ultimately ensure a maintained NT level. Such processes are ideally suited to the fast transmission effected by the amino acids and acetylcholine in some cases (nicotinic), and complements the anatomical features of their neurons and the recepter mechanisms they activate. Further, to ensure the maintenance of function in vital pathways, glutamate and GABA are stored in very high concentrations (10 pmol/mg) just as ACh is at the neuromuscular junction. 

Brailoiu, E., Patel, S. and Dun, N. J. Modulation of spontaneous transmitter release from the frog neuromuscular junction by interacting intracellular Ca2+ stores critical role for nicotinic acid-adenine dinucleotide phosphate (NAADP). Biochem. J. 373 313-318, 2003. 

Hirst I didn t make that statement. I said it didn t act as a post-junctional transmitter in a fine resistance artery. In the vein I would say that noradrenaline activates an a receptor and goes through an InsP3-dependent pathway. If you look physiologically there are clear examples where internal stores are involved in neurotransmission. What I am saying is that the places where internal stores are present seem to me to exceed the physiological requirement for them. 

ACh receptor These are located on the peaks of the junctional folds of the muscle membrane as shown. They are also found presynaptically on the nerve terminal, where, once activated, they promote migration of ACh vesicles from deep to superficial stores. 

Stuart RO, Sun A, Bush KT, and Nigam SK [1996] Dependence of epithelial intercellular junction biogenesis on thapsigargin-sensitive intracellular calcium stores. J Biol Chem 271 13636-13641... 

Schematic illustration of a generalized cholinergic junction (not to scale). Choline is transported into the presynaptic nerve terminal by a sodium-dependent choline transporter (CHT). This transporter can be inhibited by hemicholinium drugs. In the cytoplasm, acetylcholine is synthesized from choline and acetyl -A (AcCoA) by the enzyme choline acetyltransferase (ChAT). Acetylcholine is then transported into the storage vesicle by a second carrier, the vesicle-associated transporter (VAT), which can be inhibited by vesamicol. Peptides (P), adenosine triphosphate (ATP), and proteoglycan are also stored in the vesicle. Release of transmitter occurs when voltage-sensitive calcium channels in the terminal membrane are opened, allowing an influx of calcium. The resulting increase in intracellular calcium causes fusion of vesicles with the surface membrane and exocytotic expulsion of acetylcholine and cotransmitters into the junctional cleft (see text). This step can he blocked by botulinum toxin. Acetylcholine s action is terminated by metabolism by the enzyme acetylcholinesterase. Receptors on the presynaptic nerve ending modulate transmitter release. SNAPs, synaptosome-associated proteins VAMPs, vesicle-associated membrane proteins.

Nitric oxide (NO) A cotransmitter at inhibitory ENS and other neuromuscular junctions may be especially important at sphincters. Synthesized on demand by nitric oxide synthase (NOS), not stored see Chapter 19. 

Peracchia C Possible involvement of caffeine and ryanodine-sensitive calcium stores in low pH-induced regulation of gap junction channels in Peracchia C (ed) Biophysics of Gap Junction Channels. Boca Raton, CRC Press, 1991a, pp 13-28. 

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