RSK1 in Rat Neurons: A Controller of Membrane rSK2?

Eleonora Autuori,Petra Sedlak,Margreet C Ridder,Angelo Tedoldi,Li Xu,Pankaj Sah

doi:10.3389/fncir.2019.00021

Abstract

In mammalian neurons, small conductance calcium-activated potassium channels (SK channels) are activated by calcium influx and contribute to the afterhyperpolarization (AHP) that follows action potentials. Three types of SK channel, SK1, SK2 and SK3 are recognized and encoded by separate genes that are widely expressed in overlapping distributions in the mammalian brain. Expression of the rat genes, rSK2 and rSK3 generates functional ion channels that traffic to the membrane as homomeric and heteromeric complexes. However, rSK1 is not trafficked to the plasma membrane, appears not to form functional channels, and the role of rSK1 in neurons is not clear. Here, we show that rSK1 co-assembles with rSK2. rSK1 is not trafficked to the membrane but is retained in a cytoplasmic compartment. When rSK2 is present, heteromeric rSK1-rSK2 channels are also retained in the cytosolic compartment, reducing the total SK channel content on the plasma membrane. Thus, rSK1 appears to act as chaperone for rSK2 channels and expression of rSK1 may control the level of functional SK current in rat neurons.

Highlights

Potassium channels are widely expressed in the central nervous system (CNS) where they play an important role in regulating the intrinsic excitability of neurons
As shown previously (D’Hoedt et al, 2004; Church et al, 2015), transfection in Cosm6 cells shows that rat SK2 (rSK2) was expressed throughout the cell, while rSK1 tagged with HA (rSK1-HA) was restricted to the cytosolic somatic compartment (Figure 2), likely the endoplasmic reticulum and Golgi (Church et al, 2015)
We show that rSK1 channels co-assemble with rSK2, and regulate the plasma membrane levels of rSK2

Summary

Introduction

Potassium channels are widely expressed in the central nervous system (CNS) where they play an important role in regulating the intrinsic excitability of neurons. A subset of potassium channels expressed in central neurons are Ca2+-activated K+ channels that regulate cellular excitability and spike frequency adaptation (Coetzee et al, 1999; Adelman et al, 2012) These are divided into three families that comprise the large conductance (BK) channels (KCa1.1), small conductance (SK) channels KCa2.1, KCa2.2, KCa2.3 (SK1, SK2, and SK3), and the intermediate conductance (IK) channels KCa3.1 (Vergara et al, 1998). In neurons, these channels are generally driven by calcium influx during action potentials, and activation of BK currents contributes to spike repolarization, while SK channel activity is slower, contributing to the afterhyperpolarization (AHP) that follows (Sah, 1996). Functional studies in heterologous expression systems have shown that rat SK2 (rSK2) and SK3 (rSK3), and human SK1 (hSK1) channels form functional homomeric channels

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