Channel N-type

Ca channel (N-type) Ca ATPase (heart) Synaptogamin Presynaptic Ca influx Storage of Ca Release of neurotransmitters ... 

Cay2 channels (N-type) control the release of neurotransmitters at the presynaptic level. It selective blocker, ziconotide, a synthetic peptide analog of an oj-conotoxin. 

When an action potential approaches the axon terminal, voltage-gated Ca2+ channels (N-type) open and Ca2+ enters the presynapse. Ca2+ ions bind to proteins that connect the synaptic vesicle with the plasma membrane (acronym SNAP), inducing membrane fusion and consequently exocytosis of the neurotransmitter into the synaptic cleft. Botulinum b toxin contains a specific protease which interferes with synaptobrevin (a vesisle protein which interacts with the SNAP proteins) so that vesicles cannot fuse any longer. The inhibition of acetylcholine release can thus cause paralysis and death. 

Furthermore, PKCe is required for nerve growth factor-induced activation of mitogen-activated protein kinases and neurite outgrowth by ethanol. It is also required for ethanol-induced increases in N-type voltage-gated calcium channels in PC 12 neural cells. 

Other systems also interact with glutamate. Activation of L-type voltagegated calcium channels (VGCC) occurs with NMDA receptor activation. Lamotrigine blocks several ion channels, including P- and N-type VGCC channels, an action that blocks the euphoric effects of ketamine and reduces dysphoric and cognitive effects (Hundt et al. 1998). Other modulatory sites,... 

Endou M, Poli E> Levi R Histamine H3 receptor signaling in the heart possible involvement of Gj/Go proteins and N-type Ca channels. J Pharmacol Exp Ther 1994 269 221. bS... 

Figure 2.4 Noradrenergic inhibition of Ca " currents and transmitter release in sympathetic neurons and their processes, (a) Inhibition of currents through N-type Ca " channels by external application of noradrenaline (NA) or by over-expression of G-protein P y2 subunits, recorded from the soma and dendrite of a dissociated rat superior cervical sympathetic neuron. Currents were evoked by two successive 10 ms steps from —70 mV to OmV, separated by a prepulse to -1-90 mV. Note that the transient inhibition produced by NA (mediated by the G-protein Go) and the tonic inhibition produced by the G-protein Piy2 subunits were temporarily reversed by the -1-90 mV depolarisation. (Adapted from Fig. 4 in Delmas, P et al. (2000) Nat. Neurosci. 3 670-678. Reproduced with permission), (b) Inhibition of noradrenaline release from neurites of rat superior cervical sympathetic neurons by the 2-adrenoceptor stimulant UK-14,304, recorded amperometrically. Note that pretreatment with Pertussis toxin (PTX), which prevents coupling of the adrenoceptor to Gq, abolished inhibition. (Adapted from Fig. 3 in Koh, D-S and Hille, B (1997) Proc. Natl. Acad. Sci. USA 1506-1511. Reproduced with permission)...

First, their opening during somato-dendritic action potentials provides the source of the increased intracellular [Ca +] required to open Ca +-activated K+ channels — BK channels, to accelerate spike repolarisation, and SK channels, to induce spike-train adaptation and limit repetitive firing. The BK channels are activated (primarily) following entry of Ca + through L-type channels the source of Ca + for SK channel activation varies with different neurons, and may be either through L-type or N-type channels. 

The TFTs are made on transparent glass substrates, onto which gate electrodes are patterned. Typically, the gate electrode is made of chromium. This substrate is introduced in a PECVD reactor, in which silane and ammonia are used for plasma deposition of SiN as the gate material. After subsequent deposition of the a-Si H active layer and the heavily doped n-type a-Si H for the contacts, the devices are taken out of the reactor. Cr contacts are evaporated on top of the structure. The transistor channel is then defined by etching away the top metal and n-type a-Si H. Special care must be taken in that the etchant used for the n-type a-Si H also etches the intrinsic a-Si H. Finally the top passivation SiN, is deposited in a separate run. This passivation layer is needed to protect the TFT during additional processing steps. 

Mackie K, Hille B. Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc Natl Acad Sci 1992 89 3825-3829. 

G0 was isolated as an other PTx-ribosylated G-protein which co-purifies with G, but which does not inhibit adenylate cyclase. There are two main isoforms (G0l and Go2), with additional splice-variants. G0 is particularly abundant in the nervous system, comprising up to 1% of membrane proteins. Its main function is to reduce the opening probability of those voltage-gated Ca2+ channels (N- and P/Q-type) involved in neurotransmitter release. Hence, it is largely responsible for the widespread auto-inhibition of transmitter secretion by presynaptic receptors and this effect is mediated through released py subunits. 

Abbreviations 3ARK1, -adrenergic receptor kinase 1 PLC, phospholipase C GIRK, G-protein-activated inwardly rectifying potassium channel Ca(N, P, Q), N-type, P-type, or Q-type calcium channel. 

Ikeda, S. R. and Dunlap, K., Voltage-dependent modulation of N-type calcium channels role of G-protein subunits, Adv. Second Messenger Phosphoprotein Res., 33, 131-151, 1999. 

A series of 2-amino-3/4-dihydro quinazolines have been extensively explored as selective T-type calcium channel antagonists. A recent disclosure included KYS05090 (9) with an IC50 of 41 nM on the Cav3.1 subtype of the T-type channel and 120-fold selectivity versus the N-type calcium channel Cav2.2 [55]. A pharmacophore model was recently published based on this and related structures [56], but no other selectivity or in vivo activity have been disclosed since the original report. 

A structurally diverse array of N-type calcium channel antagonists has been reported, and two recent extensive reviews have summarized the structures and associated data through 2008 [59,60]. Among these... 

The benzhydryl substituent is common to many reported N-type calcium channel blockers. A recently reported series derived from the neuroepileptic flunarizine (5), which exhibits N-type calcium channel potency in a whole-cell patch-clamp assay (IC50 0.08 iM) as well as L-type potency... 

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