Calcium-dependent facilitation

Adams PJ, Garcia E, Mulatz K, Spacey SD, Snutch TP (2006) Familial Hemiplegic Migraine Mutation K1336E Differentially Affects Calcium-Dependent Facilitation Of P/Q-Type Calcium Channel Splice Variants. FENS Forum Abstracts vol. 3 A084.082. 

P/Q-type channels undergo a second calcium-dependent process whereby current activity increases following a strong membrane depolarization or a train of action potentials. This increase is only observed in the presence of external calcium, is insensitive to calcium buffers, and requires the high-affinity calcium binding sites on calmodulin (Chaudhuri et al. 2004 DeMaria et al. 2001). This process, termed calcium-dependent facilitation (CDF), is not observed with N-type or R-type channels and is Cav2.1 channel splice isoform dependent (Chaudhuri et al. 2004). The... 

Platelets can be activated by a variety of agents including the physiologic agonists ADP, thromboxane A2, epinephrine, collagen, and thrombin. Platelet activation is generally associated with a change in platelet shape (except for epinephrine-induced platelet activation) from discs to spiny spheres with pseudopodia. Platelet pseudopod formation is dependent on actin polymerization in the activated platelets. The interaction of actin filaments with myosin, mediated by calcium (9), facilitates platelet contractile activity (e.g., clot retraction). 

Pumiliotoxin B has both cardiotonic and myotonic activity in isolated atrial or rat phrenic nerve diaphragm preparations (97). The cardiotonic activity is markedly dependent on the structure of the pumiliotoxin (95). Subsequent studies on the activity of pumiliotoxin B in neuromuscular preparations were interpreted as due to an apparent facilitation of calcium translocation from internal storage sites (99 see review in Ref. 5). Inhibitory effects on the calcium-dependent ATPase of sarcoplasmic reticulum were shown to be due not to pumiliotoxin B, but to phenolic impurities, namely, fcis(2-hydroxy-3-terf-butyl-5-methylphenyl)methane, 3,5-di-/ert-butyl-4-hydroxytoluene (BHT), and nonylphenols (100). 

The oviducts of the cockroaches L. maderae (31) and P. americana (32) also contain proctolin. In both instances, quantitative estimates of proctolin-like bioactivity were made following the separation of extracts on reverse-phase HPLC. After depolarization of the tissue in high potassium saline, the proctolin-like substance in . americana was released from oviducts in a calcium dependent fashion. Oviducts in L. maderae (31) showed some responsiveness to proctolin in a calcium-free medium and the peptide also appeared to facilitate the re-entry of calcium into muscle after depleted preparations were returned to normal levels of external calcium. 

The catecholamines and serotonin share similar pathways of biosynthesis and metabolism, including in some steps, the same enzymes. Catecholamines and serotonin are sequestered and stored in vesicular granules from where they are released mto the extracellular environment by calcium-dependent exocytosis. Termination of the physiological effects of both the catecholamines and serotonin is dependent on active uptake processes, facilitated by specific... 

Further evidence for facilitation by pumiliotoxin B of calcium translocation across membranes derives from crayfish skeletal muscle (24). Pumiliotoxin B enhanced calcium-dependent action potentials in crayfish muscle with a half maximal effect at about 25 pM. Pumiliotoxin B also markedly potentiated directly evoked contractions of crayfish muscle. 

Pumiliotoxin B had calcium-dependent effects on evoked release of acetylcholine from nerve terminals in frog neuromuscular preparations 26). The alkaloid in a dose and stimulus-dependent manner caused repetitive endplate potentials in response to a single stimulation of nerve. This effect on neurotransmitter release was strongly calcium-dependent and probably involved facilitation by pumiliotoxin B of evoked calcium transport through plasma membranes and/or membranes of the endoplasmic reticulum of the nerve terminal. 

The mu, delta and kappa opioid receptors are coupled to G° and G proteins and the inhibitory actions of the opioids occur from the closing of calcium channels (in the case of the K receptor) and the opening of potassium channels (for /i, d and ORL-1). These actions result in either reductions in transmitter release or depression of neuronal excitability depending on the pre- or postsynaptic location of the receptors. Excitatory effects can also occur via indirect mechanisms such as disinhibition, which have been reported in the substantia gelatinosa and the hippocampus. Flere, the activation of opioid receptors on GABA neurons results in removal of GABA-mediated inhibition and so leads to facilitation. 

Tyrosine phosphorylation plays an important role in synaptic transmission and plasticity. Evidence for this role is that modulators of PTKs and PTPs have been shown to be intimately involved in these synaptic functions. Among the various modulators of PTKs, neuro-trophins have been extensively studied in this regard and will be our focus in the following discussion (for details of growth factors, see Ch. 27). BDNF and NT-3 have been shown to potentiate both the spontaneous miniature synaptic response and evoked synaptic transmission in Xenopus nerve-muscle cocultures. Neurotrophins have also been reported to augment excitatory synaptic transmission in central synapses. These effects of neurotrophins in the neuromuscular and central synapses are dependent on tyrosine kinase activities since they are inhibited by a tyrosine kinase inhibitor, K-252a. Many effects of neurotrophins on synaptic functions have been attributed to the enhancement of neurotransmitter release BDNF-induced increase in neurotransmitter release is a result of induced elevation in presynaptic cytosolic calcium. Accordingly, a presynaptic calcium-depen-dent phenomenon - paired pulse facilitation - is impaired in mice deficient in BDNF. 

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