Spike Ca2+ influx upmodulates the spike afterdepolarization and bursting via intracellular inhibition of KV7/M channels.
In principal brain neurons, activation of Ca(2+) channels during an action potential, or spike, causes Ca(2+) entry into the cytosol within a millisecond. This in turn causes rapid activation of large conductance Ca(2+)-gated channels, which enhances repolarization and abbreviates the spike. Here we describe another remarkable consequence of spike Ca(2+) entry: enhancement of the spike afterdepolarization. This action is also mediated by intracellular modulation of a particular class of K(+) channels, namely by inhibition of K(V)7 (KCNQ) channels. These channels generate the subthreshold, non-inactivating M-type K(+) current, whose activation curtails the spike afterdepolarization. Inhibition of K(V)7/M by spike Ca(2+) entry allows the spike afterdepolarization to grow and can convert solitary spikes into high-frequency bursts of action potentials. Through this novel intracellular modulatory action, Ca(2+) spike entry regulates the discharge mode and the signalling capacity of principal brain neurons.
Chen
Shmuel
S
Department of Physiology, Institute of Medical Sciences, Hebrew University - Hadassah Faculty of Medicine, Jerusalem 91120, Israel.
Yaari
Yoel
Y
D000200:Action Potentials / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051656:KCNQ Potassium Channels / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D015220:Calcium Channels; D002614:Chelating Agents; D051656:KCNQ Potassium Channels; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium