title: Spontaneous ryanodine-receptor-dependent Ca2+-activated K+ currents and hyperpolarizations in rat medial preoptic neurons.
abstract: The aim of the present study was to clarify the identity of slow spontaneous currents, the underlying mechanism and possible role for impulse generation in neurons of the rat medial preoptic nucleus (MPN). Acutely dissociated neurons were studied with the perforated patch-clamp technique. Spontaneous outward currents, at a frequency of approximately 0.5 Hz and with a decay time constant of approximately 200 ms, were frequently detected in neurons when voltage-clamped between approximately -70 and -30 mV. The dependence on extracellular K(+) concentration was consistent with K(+) as the main charge carrier. We concluded that the main characteristics were similar to those of spontaneous miniature outward currents (SMOCs), previously reported mainly for muscle fibers and peripheral nerve. From the dependence on voltage and from a pharmacological analysis, we concluded that the currents were carried through small-conductance Ca(2+)-activated (SK) channels, of the SK3 subtype. From experiments with ryanodine, xestospongin C, and caffeine, we concluded that the spontaneous currents were triggered by Ca(2+) release from intracellular stores via ryanodine receptor channels. An apparent voltage dependence was explained by masking of the spontaneous currents as a consequence of steady SK-channel activation at membrane potentials > -30 mV. Under current-clamp conditions, corresponding transient hyperpolarizations occasionally exceeded 10 mV in amplitude and reduced the frequency of spontaneous impulses. In conclusion, MPN neurons display spontaneous hyperpolarizations triggered by Ca(2+) release via ryanodine receptors and SK3-channel activation. Thus such events may affect impulse firing of MPN neurons.
authors.affiliation: Department of Integrative Medical Biology, Section for Physiology, Umeå University, Umeå, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Klement
authors.forename: Michael
authors.initials: M
authors.lastname: Druzin
authors.forename: David
authors.initials: D
authors.lastname: Haage
authors.forename: Evgenya
authors.initials: E
authors.lastname: Malinina
authors.forename: Peter
authors.initials: P
authors.lastname: Arhem
authors.forename: Staffan
authors.initials: S
authors.lastname: Johansson
mesh_terms: D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D047028:Macrocyclic Compounds / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010080:Oxazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002120:Calcium Channel Agonists; D002491:Central Nervous System Agents; D047028:Macrocyclic Compounds; D010080:Oxazoles; D019837:Ryanodine Receptor Calcium Release Channel; C511704:xestospongin C; D012433:Ryanodine; D002110:Caffeine; D011188:Potassium; D002118:Calcium