Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Sep 14;589(19 Pt A):2441-7.
doi: 10.1016/j.febslet.2015.06.010. Epub 2015 Jun 22.

Entropic clocks in the service of electrical signaling: 'Ball and chain' mechanisms for ion channel inactivation and clustering

Nitzan Zandany  1 , Limor Lewin  1 , Valerie Nirenberg  1 , Irit Orr  1 , Ofer Yifrach  2
Affiliations
Free article
Review

Entropic clocks in the service of electrical signaling: 'Ball and chain' mechanisms for ion channel inactivation and clustering

Nitzan Zandany et al. FEBS Lett. .
Free article

Abstract

Electrical signaling in the nervous system relies on action potential generation, propagation and transmission. Such processes are dynamic in nature and rely on precisely timed events associated with voltage-dependent ion channel conformational transitions between their primary open, closed and inactivated states and clustering at unique membrane sites. In voltage-dependent potassium (Kv) channels, fast inactivation and clustering processes rely on entropic clock chains as described by 'ball and chain' mechanisms, suggesting important roles for such chains in electrical signaling. Here, we consider evidence supporting the proposed 'ball and chain' mechanisms for Kv channel fast inactivation and clustering associated with intrinsically disordered N- and C-terminal regions of the protein, respectively. Based on this comparison, we delineate the requirements that argue for such a process and establish the thermodynamic signature of a 'ball and chain' mechanism. Finally, we demonstrate how 'chain'-level alternative splicing of the Kv channel gene modulates the entropic clock-based 'ball and chain' inactivation and clustering channel functions underlying changes in electrical signaling. As such, the Kv channel model system exemplifies how linkage between alternative splicing and intrinsic disorder enables functional diversity.

Keywords: Clustering; Entropic chain; Inactivation; Intrinsic disorder; PSD-95; Scaffold protein; Voltage-dependent potassium channel; ‘Ball and chain’.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

Substances