title: Role of small conductance Ca²⁺-activated K⁺ channels in controlling CA1 pyramidal cell excitability.
abstract: Small-conductance Ca(2+)-activated K(+) (SK or K(Ca)2) channels are widely expressed in the CNS. In several types of neurons, these channels were shown to become activated during repetitive firing, causing early spike frequency adaptation. In CA1 pyramidal cells, SK channels in dendritic spines were shown to regulate synaptic transmission. However, the presence of functional SK channels in the somata and their role in controlling the intrinsic firing of these neurons has been controversial. Using whole-cell voltage-clamp and current-clamp recordings in acute hippocampal slices and focal applications of irreversible and reversible SK channel blockers, we provide evidence that functional SK channels are expressed in the somata and proximal dendrites of adult rat CA1 pyramidal cells. Although these channels can generate a medium duration afterhyperpolarizing current, they play only an auxiliary role in controlling the intrinsic excitability of these neurons, secondary to the low voltage-activating, noninactivating K(V)7/M channels. As long as K(V)7/M channels are operative, activation of SK channels during repetitive firing does not notably affect the spike output of CA1 pyramidal cells. However, when K(V)7/M channel activity is compromised, SK channel activation significantly and uniquely reduces spike output of these neurons. Therefore, proximal SK channels provide a "second line of defense" against intrinsic hyperexcitability, which may play a role in multiple conditions in which K(V)7/M channels activity is compromised, such as hyposmolarity.
authors.affiliation: Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel.
authors.forename: Shmuel
authors.identifier: http://orcid.org/0000-0001-8843-1777
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel.
authors.forename: Felix
authors.identifier: http://orcid.org/0000-0003-3097-4693
authors.initials: F
authors.lastname: Benninger
authors.affiliation: Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel yaari@md.huji.ac.il.
authors.forename: Yoel
authors.initials: Y
authors.lastname: Yaari
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001030:Apamin / Q000494:pharmacology; D001703:Biophysics; D056547:CA1 Region, Hippocampal / Q000166:cytology*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D017966:Pyramidal Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D013997:Time Factors
chemical_list: C112297:10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; D000873:Anthracenes; D026902:Potassium Channel Blockers; D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D011189:Potassium Chloride; D015761:4-Aminopyridine
keywords: Bursting; Kv7 channels; SK channels; hippocampus; mAHP; pyramidal cell