Cholinergic efferent synaptic transmission regulates the maturation of auditory hair cell ribbon synapses

Spontaneous electrical activity generated by developing sensory cells and neurons is crucial for the maturation of neural circuits. The full maturation of mammalian auditory inner hair cells (IHCs) depends on patterns of spontaneous action potentials during a ‘critical period’ of development. The intrinsic spiking activity of IHCs can be modulated by inhibitory input from cholinergic efferent fibres descending from the brainstem, which transiently innervate immature IHCs. However, it remains unknown whether this transient efferent input to developing IHCs is required for their functional maturation. We used a mouse model that lacks the α9-nicotinic acetylcholine receptor subunit (α9nAChR) in IHCs and another lacking synaptotagmin-2 in the efferent terminals to remove or reduce efferent input to IHCs, respectively. We found that the efferent system is required for the developmental linearization of the Ca 2+ -sensitivity of vesicle fusion at IHC ribbon synapses, without affecting their general cell development. This provides the first direct evidence that the efferent system, by modulating IHC electrical activity, is required for the maturation of the IHC synaptic machinery. The central control of sensory cell development is unique among sensory systems.

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SK Current, Expressed During the Development and Regeneration of Chick Hair Cells, Contributes to the Patterning of Spontaneous Action Potentials

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.766264 ◽

2022 ◽

Vol 15 ◽

Author(s):

Snezana Levic

Keyword(s):

Electrical Activity ◽

Hair Cells ◽

Action Potentials ◽

Functional Expression ◽

Basilar Papilla ◽

Spontaneous Electrical Activity ◽

Intracellular Ca ◽

Spontaneous Action ◽

Spontaneous Action Potentials

Chick hair cells display calcium (Ca2+)-sensitive spontaneous action potentials during development and regeneration. The role of this activity is unclear but thought to be involved in establishing proper synaptic connections and tonotopic maps, both of which are instrumental to normal hearing. Using an electrophysiological approach, this work investigated the functional expression of Ca2+-sensitive potassium [IK(Ca)] currents and their role in spontaneous electrical activity in the developing and regenerating hair cells (HCs) in the chick basilar papilla. The main IK(Ca) in developing and regenerating chick HCs is an SK current, based on its sensitivity to apamin. Analysis of the functional expression of SK current showed that most dramatic changes occurred between E8 and E16. Specifically, there is a developmental downregulation of the SK current after E16. The SK current gating was very sensitive to the availability of intracellular Ca2+ but showed very little sensitivity to T-type voltage-gated Ca2+ channels, which are one of the hallmarks of developing and regenerating hair cells. Additionally, apamin reduced the frequency of spontaneous electrical activity in HCs, suggesting that SK current participates in patterning the spontaneous electrical activity of HCs.

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cAMP suppresses CA2+-dependent electrical activity of airway smooth muscle induced by TEA

Journal of Applied Physiology ◽

10.1152/jappl.1987.62.1.175 ◽

1987 ◽

Vol 62 (1) ◽

pp. 175-179 ◽

Cited By ~ 15

Author(s):

I. S. Richards ◽

J. Ousterhout ◽

N. Sperelakis ◽

C. G. Murlas

Keyword(s):

Smooth Muscle ◽

Electrical Activity ◽

Airway Smooth Muscle ◽

Action Potentials ◽

Resting Membrane Potential ◽

Airway Smooth Muscle Cells ◽

Cyclic Monophosphate ◽

Spontaneous Action ◽

Intracellular Microelectrodes ◽

Spontaneous Action Potentials

Using intracellular microelectrodes, we investigated whether exogenous dibutyryl adenosine 3 ′,5′-cyclic monophosphate (DBcAMP) or forskolin influenced the electrical effects of tetraethylammonium (TEA) on canine tracheal smooth muscle. We found that 20 mM TEA depolarized airway smooth muscle cells from a resting membrane potential (Em) of -59 +/- 4 mV (mean +/- SD) to -45 +/- 2 mV and caused spontaneous action potentials (AP's) to develop, which were 33 +/- 2 mV in amplitude. These were totally abolished in 0 Ca2+ solution. DBcAMP (1 mM) suppressed the development of this TEA-induced electrical activity and the phasic contractions electrically coupled to it. DBcAMP had no significant effect on Em in the absence of TEA however. Forskolin (1 microM) produced similar effects. Our findings suggest that Ca2+ is the principal ion responsible for the inward current associated with the TEA-induced AP's in airway smooth muscle, and that adenosine 3′,5′-cyclic monophosphate may suppress the electrogenesis of this current.

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