Somatic colocalization of rat SK1 and D class (Ca(v)1.2) L-type calcium channels in rat CA1 hippocampal pyramidal neurons.
In hippocampal neurons, the firing of a train of action potentials is terminated by generation of the slow afterhyperpolarization (AHP). Recordings from hippocampal slices have shown that the slow AHP likely results from the activation of small-conductance calcium-activated potassium (SK) channels by calcium (Ca(2+)) entry through L-type Ca(2+) channels. However, the relative localization of these two channel subtypes is not known. The cloning and characterization of three subtypes of SK channel has suggested that SK1 may underlie generation of the slow AHP. Using a novel antibody directed against rat SK1 (rSK1), it has been determined that the rSK1 channel is primarily in the soma of hippocampal CA1 neurons. In conjunction with antibodies directed against C (Ca(v)1.2) and D (Ca(v)1.3) class L-type Ca(2+) channel alpha1 subunits, it was observed that rSK1 channels were selectively colocalized with D class L-type channels. This colocalization supports the functional coupling of L-type and SK channels previously observed in cell-attached patches from hippocampal neurons. However, it appears contrary to the slow rise and decay of the slow AHP. Induction of delayed facilitation of L-type Ca(2+) channels in cell-attached patches from hippocampal neurons evoked delayed opening of coupled SK channels. Generation of ensemble currents produced waveforms identical to the ionic current underlying the slow AHP (I(sAHP)). Therefore, these data indicate that the slow AHP is somatic in origin, resulting from delayed facilitation of D class L-type Ca(2+) channels colocalized with rSK1 channels.
Bowden
S E
SE
Department of Pharmacology and Medical Research Council Center for Synaptic Plasticity, University of Bristol, Bristol, BS8 1TD, United Kingdom.
Fletcher
S
S
Loane
D J
DJ
Marrion
N V
NV
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000918:Antibody Specificity; D001923:Brain Chemistry; D020746:Calcium Channels, L-Type / Q000145:classification / Q000378:metabolism*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D015221:Potassium Channels / Q000276:immunology / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D017966:Pyramidal Cells / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels
D000906:Antibodies; D020746:Calcium Channels, L-Type; C496896:Kcnn1 protein, rat; C419385:L-type calcium channel alpha(1C); D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels