Know your current I(h): interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.

The non-specific, hyperpolarization activated, I(h) current is particularly involved in epilepsy and it exhibits an excitatory or inhibitory action on synaptic integration in an apparently inconsistent way. It has been suggested that most of the inconsistencies could be reconciled invoking an indire...

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Autores principales:	Michele Migliore, Rosanna Migliore
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/13bdd8a247b040ac8496259bf3f11403
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spelling	oai:doaj.org-article:13bdd8a247b040ac8496259bf3f114032021-11-18T07:19:05ZKnow your current I(h): interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.1932-620310.1371/journal.pone.0036867https://doaj.org/article/13bdd8a247b040ac8496259bf3f114032012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22606301/?tool=EBIhttps://doaj.org/toc/1932-6203The non-specific, hyperpolarization activated, I(h) current is particularly involved in epilepsy and it exhibits an excitatory or inhibitory action on synaptic integration in an apparently inconsistent way. It has been suggested that most of the inconsistencies could be reconciled invoking an indirect interaction with the M-type K(+) current, another current involved in epilepsy. However, here we show that the original experiments, and the simplified model used to explain and support them, cannot explain in a conclusive way the puzzling I(h) actions observed in different experimental preparations. Using a realistic model, we show instead how and why a shunting current, such as that carried by TASK-like channels, and dependent on I(h) channel is able to explain virtually all experimental findings on I(h) up- or down-regulation by modulators or pathological conditions. The model results suggest several experimentally testable predictions to characterize in more details this elusive and peculiar interaction, which may be of fundamental importance in the development of new treatments for all those pathological and cognitive dysfunctions caused, mediated, or affected by I(h).Michele MiglioreRosanna MigliorePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e36867 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michele Migliore Rosanna Migliore Know your current I(h): interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.
description	The non-specific, hyperpolarization activated, I(h) current is particularly involved in epilepsy and it exhibits an excitatory or inhibitory action on synaptic integration in an apparently inconsistent way. It has been suggested that most of the inconsistencies could be reconciled invoking an indirect interaction with the M-type K(+) current, another current involved in epilepsy. However, here we show that the original experiments, and the simplified model used to explain and support them, cannot explain in a conclusive way the puzzling I(h) actions observed in different experimental preparations. Using a realistic model, we show instead how and why a shunting current, such as that carried by TASK-like channels, and dependent on I(h) channel is able to explain virtually all experimental findings on I(h) up- or down-regulation by modulators or pathological conditions. The model results suggest several experimentally testable predictions to characterize in more details this elusive and peculiar interaction, which may be of fundamental importance in the development of new treatments for all those pathological and cognitive dysfunctions caused, mediated, or affected by I(h).
format	article
author	Michele Migliore Rosanna Migliore
author_facet	Michele Migliore Rosanna Migliore
author_sort	Michele Migliore
title	Know your current I(h): interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.
title_short	Know your current I(h): interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.
title_full	Know your current I(h): interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.
title_fullStr	Know your current I(h): interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.
title_full_unstemmed	Know your current I(h): interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.
title_sort	know your current i(h): interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/13bdd8a247b040ac8496259bf3f11403
work_keys_str_mv	AT michelemigliore knowyourcurrentihinteractionwithashuntingcurrentexplainsthepuzzlingeffectsofitspharmacologicalorpathologicalmodulations AT rosannamigliore knowyourcurrentihinteractionwithashuntingcurrentexplainsthepuzzlingeffectsofitspharmacologicalorpathologicalmodulations
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Know your current I(h): interaction with a shunting current explains the puzzling effects of its pharmacological or pathological modulations.

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