oxepins and iberiotoxin

Voltage-gated conductances on dendrites of layer 5 pyramidal neurons participate in synaptic integration and output generation. We investigated the properties and the distribution of large-conductance calcium-activated potassium channels (BK channels) in this cell type using excised patches in acute slice preparations of rat somatosensory cortex. BK channels were characterized by their large conductance and sensitivity to the specific blockers paxilline and iberiotoxin. BK channels showed a pronounced calcium-dependence with a maximal opening probability of 0.69 at 10 microm and 0.42 at 3 microm free calcium. Their opening probability and transition time constants between open and closed states are voltage-dependent. At depolarized potentials, BK channel gating is described by two open and one closed states. Depolarization increases the opening probability due to a prolongation of the open time constant and a shortening of the closed time constant. Calcium-dependence and biophysical properties of somatic and dendritic BK channels were identical. The presence of BK channels on the apical dendrite of layer 5 pyramidal neurons was shown by immunofluorescence. Patch-clamp recordings revealed a homogeneous density of BK channels on the soma and along the apical dendrite up to 850 microm with a mean density of 1.9 channels per microm(2). BK channels are expressed either isolated or in clusters containing up to four channels. This study shows the presence of BK channels on dendrites. Their activation might modulate the shape of sodium and calcium action potentials, their propagation along the dendrite, and thereby the electrotonic distance between the somatic and dendritic action potential initiation zones.

Topics: Animals; Animals, Newborn; Calcium; Dendrites; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Electric Stimulation; Immunohistochemistry; In Vitro Techniques; Indoles; Large-Conductance Calcium-Activated Potassium Channels; Membrane Potentials; Microtubule-Associated Proteins; Naphthalenes; Neocortex; Oxepins; Patch-Clamp Techniques; Peptides; Potassium Channel Blockers; Potassium Channels, Calcium-Activated; Pyramidal Cells; Rats; Rats, Wistar; Tetraethylammonium