converse look

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converse look

Messagede Benjamin Toynbee » 25 Mar 2020, 10:02

Thus, while the converse look effect of 5b on the inward currents could be explained by the direct involvement of ASICs in PSC generation as observed in the amygdala [ 5 ], the lack of an increase of the outward currents suggests that the effect of 5b is predominantly modulatory. Lack of apparent shift of estimated PSCs reversal potential (-0.75 ± 0.26 mV, n = 8) after application of 5b also supports this suggestion. (see Methods for details of estimating PSCs reversal potential). Nevertheless, to further verify this point we tried to pharmacologically isolate/enhance a fraction of synaptic current that is not mediated by GABA A -receptors (residual current) and study some of its properties.

In spite of growing evidence indicating that the density converse all star of ASICs is substantially higher in GABAergic interneurons than in glutamatergic cells [ 17 ] and recent demonstration of functional crosstalk between ASICs and GABA A -receptors [ 10 , 11 ], the possible involvement of ASICs in the regulation of converse all stars GABAergic transmission remained unclear. In our work we present evidence for the first time that ASICs play a functional role at hippocampal GABAergic synapses. This role is mediated, at least partially, by a postsynaptic but (predominantly) modulatory mechanism.We found that GABAergic postsynaptic currents, recorded below their reversal potential as inward currents, are suppressed by all the employed blockers of ASICs.

Additionally, we would like to mention that although amioloride is known to be not selective at high concentrations (for instance [ converse off white 34 ]), at concentration (25 ¼M) used in our experiments amiloride was shown to be a potent antagonist, mainly for ASIC receptors. As far as we know, diminazene is rather selective against ASICs within the time scale of our experiments (minutes). It does target DNA [ 35 ], but related consequences of this action shouldn't be expected within minutes. Indeed, we are not aware of any other than ASICs targets of diminazene, which could be responsible for  rapid' side effects.

It may be reasonably assumed, that if synaptic transmission is affected by a chemical via a purely presynaptic mechanism, similar changes of postsynaptic currents recorded below and above PSC reversal potential, would be expected. We found, however, that while GABAergic PSCs, recorded below their reversal potential as inward currents, are suppressed by all the employed ASIC blockers, in the same cells the suppression of outward off white converse currents was statistically insignificant. These results imply that the effects of blockers in our experiments are at least partially postsynaptic.

This suggestion is also indirectly supported by the observation that modulatory effect of GABA A -receptors activation on ASICs-currents can be observed in excised patches [ 10 ]. We assume that an interaction between ASICs and GABA A -receptors is quite likely to occur at GABAergic synapses upon acidification at the synaptic cleft. This assumption can be supported by the lack of the apparent effect of 5b on inward PSCS Image in the presence of bicuculline, observed in our experiments.
Benjamin Toynbee
 
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