The Molecular Basis for the Calcium-Dependent Slow Afterhyperpolarization in CA1 Hippocampal Pyramidal Neurons.

Giriraj Sahu,Ray W Turner

doi:10.3389/fphys.2021.759707

Abstract

Neuronal signal transmission depends on the frequency, pattern, and timing of spike output, each of which are shaped by spike afterhyperpolarizations (AHPs). There are classically three post-spike AHPs of increasing duration categorized as fast, medium and slow AHPs that hyperpolarize a cell over a range of 10 ms to 30 s. Intensive early work on CA1 hippocampal pyramidal cells revealed that all three AHPs incorporate activation of calcium-gated potassium channels. The ionic basis for a fAHP was rapidly attributed to the actions of big conductance (BK) and the mAHP to small conductance (SK) or Kv7 potassium channels. In stark contrast, the ionic basis for a prominent slow AHP of up to 30 s duration remained an enigma for over 30 years. Recent advances in pharmacological, molecular, and imaging tools have uncovered the expression of a calcium-gated intermediate conductance potassium channel (IK, KCa3.1) in central neurons that proves to contribute to the slow AHP in CA1 hippocampal pyramidal cells. Together the data show that the sAHP arises in part from a core tripartite complex between Cav1.3 (L-type) calcium channels, ryanodine receptors, and IK channels at endoplasmic reticulum-plasma membrane junctions. Work on the sAHP in CA1 pyramidal neurons has again quickened pace, with identified contributions by both IK channels and the Na-K pump providing answers to several mysteries in the pharmacological properties of the sAHP.

Highlights

Hippocampal CA1 pyramidal cells were one of the first central neurons to draw attention as a model for understanding the factors that control neuronal membrane excitability
To restrict recordings as much as possible to calcium-dependent potassium channels distinct from the mAHP and Na-K pump we focus on the IsAHP typically evoked by a step command or by suprathreshold repetitive spike trains of 5–10 pulses
An early report of an augmented form of NMDA-independent LTP of synaptic transmission in CA1 pyramidal cells of RyR3 KO mice may reflect a reduction in postsynaptic IsAHP potentiation, this was not tested (Futatsugi et al, 1999). Together these results reveal that sAHP potentiation can be evoked entirely by intrinsic postsynaptic mechanisms that can be selectively recruited according to specific patterns of physiologically relevant spike discharge

Summary

INTRODUCTION

Hippocampal CA1 pyramidal cells were one of the first central neurons to draw attention as a model for understanding the factors that control neuronal membrane excitability. A series of patch clamp recordings primarily in rat in vitro hippocampal slices revealed that the sAHP in CA1 pyramidal cells exhibited the complement of pharmacological properties that define IK channels (King et al, 2015) For these tests all recordings were conducted in the presence of apamin, XE-991, and CsCl to remove any contamination by SK, Kv7 or HCN channel isoforms. Potassium and 1.5 mM calcium at ∼34◦C to simulate physiological conditions, recordings revealed a channel of ∼30 pS These authors noted an apparent reduction in current amplitude and flickering at high levels of membrane polarization, as previously reported by both Lancaster et al (1991) and in studies of expressed IK channels (Ishii et al, 1997; Logsdon et al, 1997; Jensen et al, 1998). They suggest that calcium channel subtypes beyond L-type calcium channels mediate a gamma frequency-selective sAHP potentiation that can contribute to synaptic plasticity

A Cav1-RyR-IK TRIPARTITE COMPLEX DRIVES THE SLOW AFTERHYPERPOLARIZATION

Findings

DISCUSSION

CONCLUSION