A switch in the mode of the sodium/calcium exchanger underlies an age-related increase in the slow afterhyperpolarization

Abstract

During aging, the Ca 2+ sensitive slow afterhyperpolarization (sAHP) of hippocampal neurons is known to increase in duration. This change has also been observed in the serotonergic cerebral giant cells (CGCs) of the pond snail Lymnaea stagnalis, but has yet to be characterized. In this paper, we confirm that there is a reduction in firing rate, an increase in the duration of the sAHP, and an alteration in the strength and speed of spike frequency adaptation (SFA) in the CGCs during aging, a finding that is compatible with an increase in a sAHP current. We go on to show that age-related changes in the kinetics of SFA are consistent with a reduction in Ca 2+ clearance from the cell, which we confirm with Ca 2+ imaging and pharmacological manipulation of the sodium calcium exchanger (NCX). These experiments suggest that the NCX may be switching to a reverse-mode configuration in the CGCs during aging.3

Differential contributions of Ca2+‐activated K+ channels and Na+/K+‐ATPases to the generation of the slow afterhyperpolarization in CA1 pyramidal cells

“…Another source of neuronal hyperpolarization consequent to repetitive firing and massive Na + entry may be the electrogenic Na + /Ca 2+ exchanger (NCX) operating in reverse mode (Dietz et al, 2007). Indeed, this mechanism has been suggested to contribute to the sAHP increase in aging snail neurons (Scutt, Allen, Kemenes, & Yeoman, ). However, adding KB‐R7943 (10 μM), a NCX inhibitor (Iwamoto & Kita, ), to the Ni‐Cd‐aCSF had no effect on the Ca 2+ ‐independent sAHP component (Figure Ca), measured either as amplitude (1 s post‐stimulus: from −5.4 ± 0.5 to −4.7 ± 0.5 mV; p = .33; 7 s post‐stimulus: from −3.8 ± 0.8 to −3.7 ± 0.4 mV; p = .89; Figure Cb) or integral (from −60.2 ± 9.7 to −60.4 ± 10.3 mV s; p = .99; n = 5 cells, 5 slices, 5 rats; Figure Cc).…”

SK channels participate in the formation of after burst hyperpolarization and partly inhibit the burst strength of epileptic ictal discharges

“…Intracellular calcium is involved in the ABH process and burst activities. The [Ca 2+ ]i concentration is associated with the strength of AP and burst and with the activation of BK and SK channels ( 38 – 41 ). EGTA, a calcium selective chelator, was added to the pipette solution to reduce the intracellular calcium concentration.…”

What can we teach Lymnaea and what can Lymnaea teach us?

“…Further studies demonstrated that the acquisition of appetitive memory was not affected by ageing, but that memory retention and consolidation become progressively impaired with advancing age (Hermann et al ., 2007). Using appetitive classical conditioning, age‐associated learning and memory deficits were associated with declining electrophysiological excitability of the CGCs, most likely reflecting a selective deficit in the activity‐dependent regulation of gene transcription, possibly through CREB‐dependent mechanisms, as demonstrated in other models (Hermann et al ., 2007; Pirger et al ., 2010; Scutt et al ., 2015). Memory decline in aged Lymnaea is consistent with the age‐dependent impairment in learning and memory functions observed in many animal species, including humans, where the molecular, cellular, and neural network functions show a decline of neuronal experience‐dependent plasticity (Hermann et al ., 2007).…”