T-type channels

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. 

Fry The voltage dependence of these STOCs that you have shown is interesting, because there is now more evidence for T type Ca2+ currents in smooth muscle cells. Kenton Sanders, you said that it was in the window current for the L-type Ca2+ channels, but it is probably about 10 mV too negative for that. Is there any evidence that T type channel activity will be involved ... 

T-type calcium channels play critical roles in shaping the electrical and plastic properties of neurons and are also implicated in hormone secretion, differentiation and muscle development (Huguenard, 1996 Perez-Reyes, 2003). In thalamic reticular and relay neurons, T-type channels contribute to rhythmic rebound burst firing and spindle waves associated with slow-wave sleep. T-type channels also play crucial roles in dendritic integration and calcium-mediated spiking in hippocampal pyramidal cells, and in synaptic release at olfactory dendrodendritic... 

Choi S, Na HS, Kim J et al. (2007a) Attenuated pain responses in mice lacking Cav3.2 T-type channels. Genes Brain Behav 6(5) 425-431... 

In isolated DRG neurons, H2S donor (sodium hydrosulflde NaHS) facilitated T-type calcium channel-dependent currents, and caused hyperalgesia, and this effect was blocked by a T-type channel inhibitor. More results are available about the peripheral effect of H2S. H2S biosynthesis is increased following IPL injection of carrageenan, local administration of NaHS induces a mechanical hypernociception, and the hyperalgesia was decreased by H2S synthesis inhibitor or by T-type... 

The calcium channel antagonists comprise the type EV antiarrhythmic category. At least two types of calcium channels are operative in SA and AV nodal tissues an L-type channel and a T-type channel. Therefore, both L-channel blockers (verapamil and diltiazem) and selective T-channel blockers (mibefradil—previously approved but withdrawn from the market) will slow conduction, prolong refrac-... 

Several lines of evidence indicate that T-type channels are retained in sperm and are activated by ZP3 during induction of acrosome reactions... 

The T-type or low-voltage-activated calcium channels have been identified in a variety of smooth muscle cells. They activate at low membrane potentials (around -50 mV) with a maximum around -20 mV, have a small conductance (7-8 pS with 110 mM Ba2+ as charge carrier), inactivate rapidly, and are blocked by 10-100 xM Ni2+ and a variety of compounds, including some of the organic calcium channel blockers. The biological role of the T-type channels remains to be established owing to the lack of specific blockers. 

Low-voltage-activated channels or low-threshold channels, which are also termed T-type channels. 

T-type calcium channels (with the T standing for transient ) require only a weak depolarization for activation and carry a transient current at negative membrane potentials that inactivates rapidly during a prolonged pulse. In neurons, the T-type channel is responsible for neuronal oscillatory activity and is thought to play a role in the regulation of wakefulness and motor coordination. The pyrazine diuretic, amiloride, inhibits the T-type calcium channel. 

Mechanism blockade of T-type channels and thalamic neurons 0 Use absence seizures General features of anticonvulsant drug use ... 

T-type currents are difficult to record in chromaffin cells. Although we have detected T-type channel messenger (mRNA) in bovine chromafhn cells [39], we have been unable to record T-type currents. However, there are three studies reporting T-type Ca currents in bovine [40] and rat chromafhn cells [41,42]. It has been suggested that T-type Ca " channels are mainly expressed in immature developing chromafhn cells [41]. Recently, T-type channels of the ttjH class have been found to be expressed in rat chromafhn cells exposed to cyclic adenosine monophosphate (cAMP)... 

Novara M, Baldelli P, Cavallari D, Carabelli V, Giancippoli A, Carbone E. Exposure to cAMP and beta-adrenergic stimulation recruits Cav3 T-type channels in rat chromaffin cells through Epac cAMP-receptor proteins. J Physiol 2004 558(Pt 2) 433-49. 

Carbone E, Giancippoli A, Marcantoni A, Guido D, CarabeUi V. A new role for T-type channels in fast low-threshold exocytosis. Cell Calcium 2006 40(2) 147-54. 

Note L- and T-type channels are found in cardiac muscle where they are sensitive to blockade by pharmacological agents including verapamil and diltiazem... 

Likewise, a calcium channel can be changed into a sodium channel with a few tweaks,... A. Senatore et al. T-type channels become highly permeable to sodium ions using an alternative extracellular turret region (S5-P) outside the selectivity filter. 2014. / Biol Chem. 289(17), p. 11952. DOI 10.1074/jbc.M114.551473. 

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