Heat pulse excitability of vestibular hair cells and afferent neurons

Abstract

In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in <3 ms and decaying with a time constant of ∼24 ms. The inhibitory component dominated whole cell currents in 50% of hair cells at -68 mV and in 67% of hair cells at -60 mV. Responses were quantified and described on the basis of first principles of thermodynamics. Results identify key molecular targets underlying heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability.

Thermal Transients Excite Neurons through Universal Intramembrane Mechanoelectrical Effects

“…IV E and Ref. [27]), specifically allowing for the PAINTS experiment to estimate a surface charge difference that was found to be in accord with empirical values for neural cells [41].…”

“…Shapiro et al [16] showed that these rapid temperature variations are directly accompanied by changes in the cell membrane's capacitance and resulting displacement currents which are unrelated to specific ionic channels; their findings on the thermal capacitance increase have been supported by experiments from several additional groups [19,20,[23][24][25]. Shapiro et al [16] also developed a theoretical model where the temperature elevation was seen to give rise to membrane capacitance increase at the membrane's boundary regions (see also Liu et al [26] and Rabbit et al [27]). However, as recently pointed out in our reanalysis of this theoretical model [28,29], upon correcting a mathematical convention error it actually predicts a net capacitance decrease, contrary to the experimental measurements.…”

“…The model simulations take into account the contribution of two independent thermodynamic variables, temperature and membrane voltage, and the resulting displacement current is a product of the membrane effective thermoelectric capacitance (C T m ¼ ½ð∂QÞ=∂T ; see Ref. [27]) and the temperature time derivative (see Sec. IV E).…”

Millisecond infrared laser pulses depolarize and elicit action potentials on in-vitro dorsal root ganglion neurons

“…Infrared laser pulses have been shown to induce intracellular calcium transients implicating mitochondria in neonatal cardiomyocytes [10] and in neonatal spiral and vestibular ganglion neurons [11] and to depolarize membranes in HEK293 cells [12], dorsal root ganglion neurons [13], oocytes, HEK cells and artificial layers [14], retinal and vestibular primary neurons [15,16], hippocampal neurons [17], spiral ganglion neurons [18], brain slices [19] and in vestibular hair cells and afferent neurons [20]. What remains unclear is whether an universal photothermal mechanism exists and how the transient heating induced by the IR laser pulse elicits membrane depolarization of neurons and action potentials or modulates intracellular signalling.…”

BODIPY-Conjugated Xyloside Primes Fluorescent Glycosaminoglycans in the Inner Ear of Opsanus tau

“…It has been argued previously that IR heat pulses directly evoke synaptic vesicle release in addition to modulating ion channel conductance and capacitive depolarization (Rajguru et al, 2011;Liu et al, 2014;Rabbitt et al, 2016). Therefore, the expected changes in sensitivity to IR heat pulses after BX administration would be less than the changes in sensitivity to mechanical stimulation.…”