Abstract
The non-specific, hyperpolarization activated, Ih 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 Ih 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 Ih channel is able to explain virtually all experimental findings on Ih 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 Ih.
Highlights
Experimental findings on the effects of Ih modulation appear to be inconsistent
As we discuss in this paper, recent experiments and the simplified models used to explain and support them, cannot explain in a conclusive way the puzzling Ih actions observed in different experimental preparations
One of the controversial experimental findings that we will discuss here is the peak somatic depolarization reached during the activation of dendritic synaptic inputs on hippocampal CA1 pyramidal neurons, reported by George et al [5]
Summary
Experimental findings on the effects of Ih modulation appear to be inconsistent. some results can be explained in terms of Ih intrinsic properties and dendritic distribution [1], its real nature, effects, and possible interaction with other membrane mechanisms are poorly understood (discussed in [2]). A striking example of the kind of problems faced in interpreting experimental findings can be found in CA1 pyramidal neurons: induction of febrile seizures [3] or application of the anticonvulsant agent lamotrigine [4] both cause an Ih up-regulation, but result in opposite effects (excitation and inhibition with respect to control, respectively) during dendritic current injections. It has been recently suggested [5] that most of the inconsistencies among the experimental (and as well as modeling) findings related to Ih could be explained by an indirect interaction with the M-type potassium current (KM). Using a realistic model we show instead how and why a shunting current, such as that carried by TASK-like channels [12,13], dependent on the Ih peak conductance is able to explain virtually all experimental findings on Ih up- or down-regulation by modulators or pathological conditions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
