Inhibition of Na⁺/K⁺ ATPase potentiates synaptic transmission in tactile sensory neurons of the leech

Abstract

Increasing evidence indicates that modulation of Na(+)/K(+) ATPase activity is involved in forms of neuronal and synaptic plasticity. In tactile (T) neurons of the leech Hirudo medicinalis, Na(+)/K(+) ATPase is the main determinant of the afterhyperpolarization (AHP), which characterizes the firing of these mechanosensory neurons. Previously, it has been reported that cAMP (3',5'-cyclic adenosine monophosphate), which mediates the effects of serotonin (5HT) in some forms of learning in the leech, negatively modulates Na(+)/K(+) ATPase activity, thereby reducing the AHP amplitude in T neurons. Here, we show that a transient inhibition of Na(+)/K(+) ATPase can affect the synaptic connection between two ipsilateral T neurons. Bath application of 10 nm dihydroouabain (DHO), an ouabain analogue, causes an increase in the amplitude of the synaptic potential (SP) recorded in the postsynaptic element when a test stimulus is applied in the presynaptic neuron. Iontophoretic injection of cAMP into the presynaptic T neuron also produces an increase of SP. Simulations carried out by using a computational model of the T neuron suggest that a reduction of the pump rate and a consequent depression of the AHP might facilitate the conduction of action potentials to the synaptic terminals. Moreover, nearly intact leeches injected with 10 nm DHO respond with a swimming episode more quickly to an electrical stimulation, which selectively activates T neurons exhibiting sensitization of swimming induction. Collectively, our results show that inhibition of Na(+)/K(+) ATPase is critical for short-term plasticity.

FXYD2, a γ subunit of Na+,K+-ATPase, maintains persistent mechanical allodynia induced by inflammation

“…This function of FXYD2 provides a considerable scope for regulation of the membrane potential by changing the number of this γ subunit in the NKA complex or by altering the biochemical properties or protein conformation of FXYD2. Previous studies have shown that a relatively small change in the membrane potential by modulating the NKA activity can markedly affect the synaptic transmission [33]. We found that loss of FXYD2 increased the number of small DRG neurons with a low frequency of AP firing, and it reduced the sEPSC frequency in the dorsal spinal cord.…”

Ionic mechanisms underlying history-dependence of conduction delay in an unmyelinated axon

“…We show that the STS effect is due to the Na + /K + pump (Figure 3). It has been proposed for many axons that slow hyperpolarization and slowing of conduction is caused by this pump, which is activated by the massive Na + influx during repetitive spiking and causes a net deficit of positive charge (Van Essen, 1973; Gordon et al, 1990; Bostock and Bergmans, 1994; Robert and Jirounek, 1994; Vagg et al, 1998; Baker, 2000; Kiernan et al, 2004; Moldovan and Krarup, 2006; Scuri et al, 2007). Direct experimental evidence of the involvement of the pump in activity-dependent dynamics for the PD axon is missing because of the difficulty that pharmacological block of the pump also interferes with its overall role in maintaining a functional membrane potential (Ballo and Bucher, 2009).…”

Intracellular calcium dynamics permit a Purkinje neuron model to perform toggle and gain computations upon its inputs

“…Relevantly, a mutation in the Na + /K + pump causes rapid-onset dystonia-parkinsonism (RDP), which has symptoms to indicate that it is a pathology of cerebellar computation (Cannon, 2004; de Carvalho et al, 2004). Indeed, there is a growing body of work showing that Na + /K + pumps might subserve information processing roles in neurons (Arganda et al, 2007; Scuri et al, 2007; Forrest, 2008; Forrest et al, 2009, 2012; Pulver and Griffith, 2010; Zhang and Sillar, 2012). For cerebellar Purkinje cells, we speculate that the Na + /K + pump is not simply a homeostatic mechanism to ionic gradients; we venture that it is a computational element.…”