BDNF induces calcium elevations associated with IBDNF, a nonselective cationic current mediated by TRPC channels

Area of Science:

• Neuroscience
• Molecular Biology
• Cellular Physiology

Background:

• Brain-derived neurotrophic factor (BDNF) significantly impacts hippocampal neurons.
• The precise mechanisms initiating BDNF's cellular effects remain largely unknown.
• Understanding BDNF signaling is crucial for neurodegenerative disease research.

Purpose of the Study:

• To elucidate the signaling pathways mediating BDNF's actions on hippocampal neurons.
• To identify the ion channels responsible for BDNF-induced intracellular calcium changes.
• To investigate the role of TRPC channels in BDNF-evoked neuronal responses.

Main Methods:

• Localized application of BDNF to CA1 pyramidal neuron dendrites.
• Measurement of intracellular calcium (Ca2+) concentrations.
• Electrophysiological recordings to detect cationic currents (I(BDNF)).
• Pharmacological inhibition of TRPC channels using SKF-96365.
• Assessment of Trk, IP3 receptors, and intracellular calcium store involvement.

Main Results:

• BDNF application induced transient intracellular Ca2+ elevations independent of depolarization or NMDAR activation.
• These Ca2+ signals were consistently linked to a sustained nonselective cationic current (I(BDNF)).
• The current and Ca2+ elevations were mediated by Transient Receptor Potential Canonical (TRPC3) channels.
• Inhibition of TRPC channels blocked BDNF-induced Ca2+ signals and I(BDNF).

Conclusions:

• TRPC channels are novel mediators of BDNF-induced intracellular calcium elevations.
• BDNF signaling in hippocampal neurons involves sustained cationic membrane currents through TRPC channels.
• This discovery provides new insights into the molecular mechanisms of BDNF action.