Ca2+ influx

In the following, the cardiac action potential is explained (Fig. 1) An action potential is initiated by depolarization of the plasma membrane due to the pacemaker current (If) (carried by K+ and Na+, which can be modulated by acetylcholine and by adenosine) modulated by effects of sympathetic innervation and (3-adrenergic activation of Ca2+-influx as well as by acetylcholine- or adenosine-dependent K+-channels [in sinus nodal and atrioventricular nodal cells] or to dqjolarization of the neighbouring cell. Depolarization opens the fast Na+ channel resulting in a fast depolarization (phase 0 ofthe action potential). These channels then inactivate and can only be activated if the membrane is hyperpolarized... 

Cataract formation Ca2+ influx activates m-calpain, the predominant calpain in lens, cleaving a- and 3- but not y-crystallins. The cry stall in fragments aggregate to form cataracts39... 

Dihydropyridine receptor (DHPR) is a member of voltage-dqiendent Ca2+ channels (CaVi, L-type), which specifically binds to dihydropyridine derivatives, a group of the Ca2+ channel blockers. Cav 1.1 works as the voltage sensor for skeletal muscle contraction, and Cay 1.2, as Ca2+-influx channel for cardiac muscle contraction. 

Transduction mechanism Inhibition of adenylyl cyclase stimulation of tyrosine phosphatase activity stimulation of MAP kinase activity activation of ERK inhibition of Ca2+ channel activation stimulation of Na+/H+ exchanger stimulation of AM PA/kainate glutamate channels Inhibition of forskol in-stimulated adenylyl cyclase activation of phos-phoinositide metabolism stimulation of tyrosine phosphatase activity inhibition of Ca2+ channel activation activation of K+ channel inhibition of AM PA/ kainate glutamate channels inhibition of MAP kinase activity inhibition of ERK stimulation of SHP-1 and SHP-2 Inhibition of adenylyl cyclase stimulation of phosphoinositide metabolism stimulation of tyrosine phosphatase activation of K+ channel inhibi-tion/stimulation of MAP kinase activity induction of p53 and Bax Inhibition of adenylyl cyclase stimulation of MAP kinase stimulation of p38 activation of tyrosine phosphatase stimulation of K+ channels and phospholipase A2 Inhibition of adenylyl cyclase activation/ inhibition of phosphoinositide metabolism inhibition of Ca2+ influx activation of K+ channels inhibition of MAP kinase stimulation of tyrosine phosphatase... 

The founding member of the TRP channel family, TRP, was identified as the product of a gene locus, which was referred to a transient receptor potential (TRP), because TRP mutant flies display a defect in light induced Ca2+ influx. 

Human platelets Platelet activation and aggregation by inducing Ca2+ influx [112]... 

Semberova, J. et al. (2009) Carbon nanotubes activate blood platelets by inducing extracellular Ca2 + influx sensitive to calcium entry inhibitors. Nano Letters, 9 (9), 3312-3317. 

Ca2+ influx initiates protein and membrane associations by several different mechanisms. Allosteric regulation of the hydrophobicity of protein-binding surfaces frequently occurs. One of the best studied examples is the Ca2+-dependent binding of calmodulin to other proteins (Ch. 22). Annexins are a family of proteins that exhibit Ca2+-dependent associations with cell membranes through direct interaction with phospholipids, and conversely, interactions with phospholipids increase their affinities for Ca2+ [7]. 

Voltage-gated Ca2+ channels Mediate Ca2+ influx for neurotransmitter release at the active zone. 

Presynaptic events during synaptic transmission are rapid, dynamic and interconnected. The time between Ca2+ influx and exocytosis in the nerve terminal is very short. At the frog NMJ at room temperature, 0.5-1 ms elapses between the depolarization of the nerve terminal and the beginning of the postsynaptic response. In the squid giant synapse, recordings can be made simultaneously in the presynaptic nerve terminal and in the postsynaptic cell. Voltage-sensitive Ca2+ channels open toward the end of the action potential. The time between Ca2+ influx and the postsynaptic response as measured by the postsynaptic membrane potential is 200 ps (Fig. 10-7). However, measurements made with optical methods to record presynaptic events indicate a delay of only 60 ps between Ca2+ influx and the postsynaptic response at 38°C [21]. 

The short delays between Ca2+ influx and exocytosis have important implications for the mechanism of fusion of synaptic vesicles (see Ch. 9). In this short time, a synaptic vesicle cannot move significant distances and must be already at the release site. From the diffusion constant of Ca2+ in squid axoplasm, one can calculate that Ca2+ could diffuse a distance of only 850 A, somewhat greater than the diameter of a synaptic vesicle. Therefore, in fast synapses, vesicle exocytosis sites must be close to the triggering Ca2+ channels.. Vesicles are exposed to [Ca2+] of a few hundred micromoles near the cytoplasmic mouth of the channels. 

FIGURE 10-7 The delay between Ca2+ influx into the nerve terminal and the postsynaptic response is brief. The temporal relationships between the Ca2+ current and the action potential in the nerve terminal and the postsynaptic response in the squid giant synapse are shown. The rapid depolarization (a) and repolarization (b) phases of the action potential are drawn. A major fraction of the synaptic delay results from the slow-opening, voltage-sensitive Ca2+ channels. There is a further delay of approximately 200 is between Ca2+ influx and the postsynaptic response. (With permission from reference [20].)... 

In transfected cells, H3 receptor mediated activation of Gj/0 proteins has also been reported to modulate arachi-donic acid release [29] and the Na+/H+ exchanger [44], and to inhibit Ca2+ influx and exocytosis of [3H] noradrenaline from transfected SH-SY5Y-H3 cells [45], The inhibition of Ca2+ influx may be particularly relevant in view of the known physiological function of the brain H3 receptor. 

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