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1. Introduction
2. Lecture overview
3. Auditory pathway
4. Ion channels initiate sound transmission
5. Voltage-gated Ca2+ channels trigger signaling
6. Voltage-gated Ca2+ channels
7. Measurements of Ca2+ currents (1)
8. Measurements of Ca2+ currents (2)
9. Which channels expressed in inner hair cells?
10. Cav1.3 the primary Cav in mouse inner hair cells
11. Hearing is affected without Cav1.3 channels
12. Mice lacking Cav1.3 are deaf
13. Loss of Cav1.3 also causes cardiac arrhythmia
14. LOF of Cav1.3 causes deafness in humans
15. Deafness-causing mutation in CACNA1D
16. Congenital hearing loss in homozygous carriers
17. CACNA1D mutation causes cardiac arrhythmia
18. How does CACNA1D mutation cause deafness?
19. Glycine insertion occurs in a conserved region
20. Testing the functional effects of the insertion
21. Glycine insertion blocks Cav1.3 function
22. Why are mutant channels non-functional?
23. Measuring gating currents
24. Mutant channels do not conduct Ca2+ ions
25. Cav1.3 LOF causes deafness in mice and humans
26. What about Cav1.3 gain-of-function?
27. The harmonin gene
28. Cav1.3 interacts with PDZ-proteins
29. Harmonin binds to Cav1.3
30. The functional effects of harmonin on Cav1.3
31. Harmonin inhibits Cav1.3 current density
32. Harmonin regulate synaptic Cav1.3 channels
33. dfcr-harmonin does not interact with Cav1.3
34. Harmonin regulate Cav1.3 in inner hair cells
35. Harmonin inhibits Cav1.3 currents
36. How does harmonin inhibit Cav1.3?
37. Proteosomal degradation controls protein levels
38. MG132 reverses harmonin inhibition of Cav1.3
39. Regulation of Cav1.3 by harmonin at synapse
40. Function of Cav1.3 is necessary for hearing
41. Acknowledgements

Topics Covered

• Auditory transmission
• Voltage-gated Ca(v) Ca2+ channels
• Role of Ca(v)1.3 in auditory hair cells
• How alterations in Ca(v)1.3 may cause deafness

Links

Series:

• Calcium Signaling II

Categories:

• Biochemistry
• Cell Biology
• Neuroscience

Therapeutic Areas:

• Neurology

Talk Citation

Publication History

• Published on October 31, 2012

Financial Disclosures

• Dr. Amy Lee has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.