title: The role of small-conductance Ca2+-activated K+ channels in the modulation of 4-aminopyridine-induced burst firing in rat cerebellar Purkinje cells.
abstract: Small-conductance Ca(2+)-activated K(+) channels (SK) regulate the firing properties of many types of neurons. In the mammalian brain, 3 subunits (SK1-SK3) are expressed with different distributions. Purkinje cells (PCs), the central neuron of the cerebellar basic circuit, express the SK2 subunit in their soma and dendrites. Mature PCs fire bursts of Na(+)-Ca(2+) spikes that constitute the sole output of the cerebellar cortex. Application of 4-aminopyridine (4-AP), blocker of Kv potassium channels in brain slices, augments the electrical activity and burst firing in mature PCs. Using conventional intracellular recordings from acutely prepared brain slices, we examined the role of SK channels in regulation of the 4-AP-induced burst activity in PCs. Application of apamin, blocker of the SK channels induced a depolarization in the membrane potential particularly between spontaneous bursts induced by 4-AP. To study the role of SK channels in 4-AP-induced burst, the spontaneous activity was suppressed by injecting adequate hyperpolarizing current and the bursts were evoked by depolarizing pulse. Apamin decreased the duration of the evoked bursts in 4-AP-treated neurons. It also prolonged the duration and repolarization time of the Ca(2+) spikes and decreased the number of and interval between Na(+) spikes in the 4-AP-induced bursts. Decrease in interval between Na(+) spikes was also seen in the rebound responses. Our findings suggest that SK channels are active at membrane potentials close to resting membrane potential in mature PCs and play an important role in the regulation of neuronal hyperexcitability and burst firing.
authors.affiliation: Neuroscience Research Center and Department of Physiology, Shaheed Beheshti Medical Sciences University, Tehran, Iran.
authors.forename: Hashem Haghdoost
authors.initials: HH
authors.lastname: Yazdi
authors.forename: Mahyar
authors.initials: M
authors.lastname: Janahmadi
authors.forename: Gila
authors.initials: G
authors.lastname: Behzadi
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012964:Sodium / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D051640:Small-Conductance Calcium-Activated Potassium Channels; D001030:Apamin; D012964:Sodium; D015761:4-Aminopyridine; D002118:Calcium