Senior Scientist and Principal Investigator: John Adelman
Current Lab Members
Research Assistant 2
Lab Phone Number:
John Adelman Lab
Vollum Institute, L474
Oregon Health & Science University
3181 SW Sam Jackson Park Rd.
Portland, OR 97239-3098
These are some of the projects currently underway in the lab.
SK channels are Ca-activated K channels, gated solely by intracellular Ca ions. SK channels are constitutively associated with calmodulin (CaM) that binds to the CaMBD in the intracellular C-terminus of the channels. When Ca ions bind to the N-lobe E-F hands of CaM, a gating transition is initiated, the gate of the channel opens and K flows through the channel pore, exerting a repolarizing influence on the membrane potential.
In hippocampal CA1 neurons in culture, transfected with externally epitope-tagged SK2 channels, and GFP for contrast, live cell immunostaining reveals SK2 expression throughout the dendrites and in dendritic spines.
In dendritic spines SK2 channels form a Ca-mediated feedback loop with NMDA receptors. Upon synaptic stimulation Ca entering through NMDAr, critical to synaptic plasticity, activates nearby SK2 channels. The repolarizing effect of SK2 channel activity opposes the AMPAr mediate depolarization and attenuates Mg unblock of NMDAr, thereby limiting Ca entry through NMDAr and altering the threshold for the induction of synaptic plasticity. Therefore, application of apamin, a selective SK channel blocker, increases synaptically evoked EPSPs and the increase is blocked by blocking NMDAr with AP5.
The model described above requires co-localization of NMDAR and SK2 channels in the postsynaptic density (PSD). Post-embedding double label immunogold electron microscopy reveals that NMDAr and SK2 channels are co-distributed within the PSD.
In addition to modulating synaptic responses, SK2 channels contribute to LTP. Upon the induction of LTP AMPAr density in the PSD is increased while SK2 channels are removed due to PKA phosphorylation of three serine residues in the SK2 C-terminal domain. Therefore, the increase depolarizing AMPAr contribution and the decreased SK2 repolarizing contribution sum together to result in the increased EPSP that is the hallmark of LTP.