Dynamic remodeling of the ionic basis of an intrinsic inhibitory response by the phospholipid PIP2
Date
2020-09-22
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Abstract
The excitability of an individual neuron can be directly related to the different types of potassium channels it expresses. Potassium channels that are activated by either calcium or voltage contribute to a wide range of physiological processes and many cognitive impairments if mutated or disrupted. A key mechanism to regulate neuronal activity is to generate afterhyperpolarizations (AHPs). AHPs are brief inhibitory periods that span from a fast (ms) to slow (sec) time frame. A voltage and calcium-gated potassium channel (Kv7) and an intermediate conductance calcium-gated potassium channel (IK) in CA1 hippocampal pyramidal cells hyperpolarize the cell by generating a medium and slow AHP. The availability of at least Kv7 channels can be modulated by a phosphatidylinositol molecule (PIP2). We measured the relative activity of each potassium channel using whole-cell patch recordings in rat hippocampal tissue slices maintained in vitro and in the tsA-201 heterologous expression system. Both channels prove to be activated by calcium increases derived from a combination of Cav1.3 channels and ryanodine receptor 2. However, modulating PIP2 levels produced opposite effects on coexpressed Kv7.2/3 and IK-mediated outward currents. Super resolution microscopy of immunolabeled proteins in cultured hippocampal neurons revealed a novel close association between Kv7.2 and IK potassium channels in somatic and dendritic membranes. The ability for PIP2 to reverse the roles of Kv7.2/3 and IK channels in producing a medium/slow AHP identifies a novel mechanism by which the ionic basis of inhibitory responses can be dynamically modulated to control intrinsic excitability in CA1 pyramidal cells.
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Keywords
IKCa, Kv7, mAHP, sAHP, PIP2
Citation
Nicholls, S. (2020). Dynamic remodeling of the ionic basis of an intrinsic inhibitory response by the phospholipid PIP2 (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.