Abstract
Previous experimental data indicates the hyperpolarization‐activated cation (I h) current, in the inner ear, consists of two components [different hyperpolarization‐activated cyclic nucleotide‐gated (HCN) subunits] which are impossible to pharmacologically isolate. To confirm the presence of these two components in vestibular ganglion neurons we have applied a parameter identification algorithm which is able to discriminate the parameters of the two components from experimental data. Using simulated data we have shown that this algorithm is able to identify the parameters of two populations of non‐inactivated ionic channels more accurately than a classical method. Moreover, the algorithm was demonstrated to be insensitive to the key parameter variations. We then applied this algorithm to I h current recordings from mouse vestibular ganglion neurons. The algorithm revealed the presence of a high‐voltage‐activated slow component and a low‐voltage‐activated fast component. Finally, the electrophysiological significance of these two I h components was tested individually in computational vestibular ganglion neuron models (sustained and transient), in the control case and in the presence of cAMP, an intracellular cyclic nucleotide that modulates HCN channel activity. The results suggest that, first, the fast and slow components modulate differently the action potential excitability and the excitatory postsynaptic potentials in both sustained and transient vestibular neurons and, second, the fast and slow components, in the control case, provide different information about characteristics of the stimulation and this information is significantly modified after modulation by cAMP.
Highlights
The identification and characterisation of neuronal ionic conductances remains a major component of electrophysiological research
The results suggest that the fast and the slow components modulate differently action potential (AP) excitability and excitatory postsynaptic potentials (EPSPs) in the sustained and transient vestibular ganglion neurons
This study shows that the indicates the hyperpolarization-activated cation (Ih) current in vestibular ganglion neurons is composed of a slow and a fast component which are activated at different voltages, quite similar to the Ih current in the guinea pig spiral ganglion (Chen, 1997), the rat primary auditory afferent dendrites (Yi et al, 2010) and the vestibular calyx afferent of Mongolian gerbils (Meredith et al, 2012)
Summary
The identification and characterisation of neuronal ionic conductances remains a major component of electrophysiological research. The corresponding current response is fitted in order to identify its magnitude and time constant parameters (Hodgkin & Huxley, 1952). This method extracts these characteristics from each voltage-clamp trace independently. An improved method that simultaneously extracts the conductance characteristics using all voltage-clamp traces at once has been shown to produce more accurate solutions in the identification of sodium currents (Willms et al, 1999). This algorithm is called the full-trace method
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