Dopaminergic modulation of axon initial segment calcium channels regulates action potential initiation.
Action potentials initiate in the axon initial segment (AIS), a specialized compartment enriched with Na(+) and K(+) channels. Recently, we found that T- and R-type Ca(2+) channels are concentrated in the AIS, where they contribute to local subthreshold membrane depolarization and thereby influence action potential initiation. While periods of high-frequency activity can alter availability of AIS voltage-gated channels, mechanisms for long-term modulation of AIS channel function remain unknown. Here, we examined the regulatory pathways that control AIS Ca(2+) channel activity in brainstem interneurons. T-type Ca(2+) channels were downregulated by dopamine receptor activation acting via protein kinase C, which in turn reduced neuronal output. These effects occurred without altering AIS Na(+) or somatodendritic T-type channel activity and could be mediated by endogenous dopamine sources present in the auditory brainstem. This pathway represents a new mechanism to inhibit neurons by specifically regulating Ca(2+) channels directly involved in action potential initiation.
Oregon Hearing Research Center, Oregon Health and Science University, Portland, OR 97239, USA. benderke@ohsu.edu
Kevin J
KJ
Bender
Christopher P
CP
Ford
Laurence O
LO
Trussell
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology*; D020747:Calcium Channels, T-Type / Q000502:physiology*; D017626:Cochlear Nucleus / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D004563:Electrochemistry; D004594:Electrophysiology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008813:Mice, Inbred ICR; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011954:Receptors, Dopamine / Q000502:physiology; D050637:Receptors, Dopamine D3 / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology
D020747:Calcium Channels, T-Type; D015221:Potassium Channels; D011954:Receptors, Dopamine; D050637:Receptors, Dopamine D3; D015222:Sodium Channels; D011493:Protein Kinase C; D004298:Dopamine