Calcium-Induced Calcium Release during Action Potential Firing in Developing Inner Hair Cells

by Radu Iosob, Daniele Avitabile, Lisa Grant, Krasimira Tsaneva-Atanasova, and Helen J. Kennedy
https://doi.org/10.1016/j.bpj.2014.11.3489

- They studied how Ca²⁺-induced Ca²⁺ release (CICR) contributes to the spiking activity of an inner hair cell.

- CICR is a quite ubiquitous mechanism for amplification in the intracellular signaling cascade. A brief increase in intracellular calcium triggers calcium release from sarcoplasmic reticulum through ryanodine-sensitive channels (RyRs). This cascade is often triggered by the Ca²⁺  influx of from extracellular space through voltage-gated Ca²⁺ channels

- They concluded that CICR plays a pivotal role in shaping action potentials through activating the SK2 channel. SK2 is a calcium-dependent potassium channel. Blockade of CICR or SK2 broadens the spikes.

- They also stated that CICR indirectly affects the amount of transmitter release by changing the spike duration. However, they concluded that it has no direct effect on the transmitter release machinery at the presynaptic terminal.


-  They performed only a few electrophysiological experiments with ryanodine of two different concentrations. And then mathematical modeling. Nevertheless, this is a straightforward paper — a good read for early learners studying signal transduction of sensory neurons.

Shakiryanova's vesicle mobility paper (2007)

It has been postulated that vesicle mobility is increased to enhance release of transmitters, its mechanism was unknown.

Ryanodine receptor mediated Ca2+-induced Ca2+ release from ER is necessary for the sustained DCV mobilization.
This RyR-receptor mediated release is short-lived, and triggers activation of CaMKII as a downstream activator.

ryanodine (high purity) and other chemicals were purchased from Calbiochem.

4-bromo-clacimycin is a Ca2+ ionophore.

cytosolic calcium sensor, Cameleon 2.1.

CaMKII activity can be blocked by a membrane-permiable version of AIP-II (Antennapedia peptide fused).

veratridine, a sodium channel opener (that results in an increase of intracellular Ca2+).