References of "Marrion, Neil"
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See detailIon channel modulators: more diversity than previously thought
Dilly, Sébastien ULg; Lamy, Cédric; Marrion, Neil et al

in Chembiochem : A European Journal of Chemical Biology (2011), 12(12), 1808-1812

Ion channel function can be modified in various ways. For example, numerous studies have shown that currents through voltage-gated ion channels are affected by pore block or modification of voltage ... [more ▼]

Ion channel function can be modified in various ways. For example, numerous studies have shown that currents through voltage-gated ion channels are affected by pore block or modification of voltage-dependence of activation/inactivation. Recent experiments performed on various ion channels show that allosteric modulation is an important mechanism to affect channel function. For instance, in KCa2 (formerly SK) channels, the prototypic “blocker” apamin prevents conduction by an allosteric mechanism, while TRPV1 channels are prevented from closing by a tarantula toxin, DkTx, through an interaction with residues located away from the selectivity filter. The recent evidence therefore suggests that, in several ion channels, the region around the outer mouth of the pore is rich in binding sites which may be exploited therapeutically. These discoveries also suggest that the pharmacological vocabulary should be adapted to define these various actions. [less ▲]

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See detailCrucial role of a shared extracellular loop in apamin sensitivity and maintenance of pore shape of small-conductance calcium-activated potassium (SK) channel
Weatherall, Kate; Seutin, Vincent ULg; Liégeois, Jean-François ULg et al

in Proceedings of the National Academy of Sciences of the United States of America (2011), 108(45), 18488-18493

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See detailInhibition of KCa 2.2 and KCa 2.3 channel currents by protonation of outer pore histidine residues
Goodchild, Samuel; Lamy, Cédric ULg; Seutin, Vincent ULg et al

in Journal of General Physiology (2009), 134(4), 295-308

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See detailDirect block of SK2 and SK3 current by the sigma agonist 1,3-di-(2-tolyl)guanidine
Lamy, Cédric; Moreau, Jacqueline ULg; Dilly, Sébastien ULg et al

Poster (2008, November 17)

Sigma receptors are widely distributed in the central nervous system where they modulate neurotransmitter release, receptor function, ionic channel activity and calcium homeostasis. Two subtypes of sigma ... [more ▼]

Sigma receptors are widely distributed in the central nervous system where they modulate neurotransmitter release, receptor function, ionic channel activity and calcium homeostasis. Two subtypes of sigma receptors have been identified (sigma-1 and sigma-2) with different pharmacological profiles, anatomical distribution and physiological functions. 1,3-Di-(2-tolyl)guanidine (DTG) is a sigma-1 and sigma-2 agonist which is widely used to probe the function of these receptors. It has recently been shown that sigma-1 receptor activation reduces the opening of SK channels in the hippocampus. We have observed that DTG (100 µM) reduces the apamin-sensitive afterhyperpolarization (AHP) of dopaminergic neurons within a slice preparation by ~60%, an effect not observed with other sigma agonists. In addition, neither the selective sigma-1 antagonist BD 1047 (30 µM) nor haloperidol (1 µM) blocked the effect of DTG, which suggested that the inhibition of the AHP might result from a direct block of the underlying SK channels. Whole-cell recordings were made from HEK293 cells transiently transfected with rSK2 or hSK3 cDNA in symmetrical K+ conditions with currents activated by a [Cai] of 1 µM. Expressed SK2 and SK3 channels displayed a classical pharmacology, being blocked by apamin with mean IC50’s of 100 pM and 4 nM, respectively. In contrast, both channel subtypes were blocked with equal sensitivity by N-methyl-laudanosine (NML). DTG inhibited both SK2 and SK3 currents with the same potency (IC50’s were ~30 µM). A mutation that rendered both SK2 and SK3 insensitive to apamin and NML produced a current that was still sensitive to DTG. This direct block of SK channels may be important to consider in relation to the pharmacological effects of this compound. [less ▲]

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