1,720,984 research outputs found
Developmental Regulation of Small-Conductance Ca²⁺-Activated K⁺ Channel Expression and Function in Rat Purkinje Neurons
No full textCalcium transients play an important role in the early and later phases of differentiation and maturation of single neurons and neuronal networks. Small-conductance calcium-activated potassium channels of the SK type modulate membrane excitability and are important determinants of the firing properties of central neurons. Increases in the intracellular calcium concentration activate SK channels, leading to a hyperpolarization of the membrane potential, which in turn reduces the calcium inflow into the cell. This feedback mechanism is ideally suited to regulate the spatiotemporal occurrence of calcium transients. However, the role of SK channels in neuronal development has not been addressed so far. We have concentrated on the ontogenesis and function of SK channels in the developing rat cerebellum, focusing particularly on Purkinje neurons. Electrophysiological recordings combined with specific pharmacological tools have revealed for the first time the presence of an afterhyperpolarizing current (I_{AHP}) in immature Purkinje cells in rat cerebellar slices. The channel subunits underlying this current were identified as SK2 and localized by in situ hybridization and subunit-specific antibodies. Their expression level was shown to be high at birth and subsequently to decline during the first 3 weeks of postnatal life, both at the mRNA and protein levels. This developmental regulation was tightly correlated with the expression of I_{AHP} and the prominent role of SK2 channels in shaping the spontaneous firing pattern in young, but not in adult, Purkinje neurons. These results provide the first evidence of the developmental regulation and function of SK channels in central neurons
Properties of the medium afterhyperpolarization and firing pattern modulation of interneurons in stratum radiatum of the CA3 hippocampal region.
No full textChemical anoxia activates ATP-sensitive and blocks Ca2+- dependent K+ channels in rat dorsal vagal neurons in situ
No full textThe contribution of subclasses of K+ channels to the response of mammalian neurons to anoxia is not yet clear. We investigated the role of ATP-sensitive (K-ATP) and Ca2+- activated K+ currents (small conductance, SK, big conductance, BK) in mediating the effects of chemical anoxia by cyanide, as determined by electrophysiological analysis and fluorometric Ca2+ measurements in dorsal vagal neurons of rat brainstem slices. The cyanide-evoked persistent outward current was abolished by the KATP channel blocker tolbutamide, but not changed by the SK and BK channel blockers apamin or tetraethylammonium. The K+ channel blockers also revealed that ongoing activation of K-ATP and SK channels counteracts a tonic, spike-related rise in intracellular Ca2+ ([Ca2+](i)) under normoxic conditions, but did not modify the rise of [Ca2+](i) associated with the cyanide-induced outward current. Cyanide depressed the SK channel-mediated afterhyperpolarizing current without changing the depolarization-induced [Ca2+](i) transient, but did not affect spike duration that is determined by BK channels. The afterhyperpolarizing current and the concomitant [Ca2+](i) rise were abolished by Ca2+-free superfusate that changed neither the cyanide-induced outward current nor the associated [Ca2+](i) increase, Intracellular BAPTA for Ca2+ chelation blocked the afterhyperpolarizing current and the accompanying [Ca2+](i) increase, but had no effect on the cyanide-induced outward current although the associated [Ca2+](i) increase was noticeably attenuated. Reproducing the cyanide-evoked [Ca2+](i) transient with the Ca2+ pump blocker cyclopiazonic acid did not evoke an outward current. Our results show that anoxia mediates a persistent hyperpolarization due to activation of KATP channels, blocks SK channels and has no effect on BK channels, and that the anoxic rise of [Ca2+](i) does not interfere with the activity of these K I channels. (C) 2002 IBRO. Published by Elsevier Science Ltd. All rights reserved
Developmental expression of AHP currents and SK channel subunits in rat hippocampal pyramidal neurons
No full textDevelopmental Regulation of Small Conductance Calcium-Activated Potassium Channel Expression and Function in Rat Purkinje Neurons
No full textTemporal and spatial patterns of expression of SK channel subunits in the developing rat brain
No full textDevelopmental Regulation of AHP Currents and SK Channel Subunit Expression in Hippocampal Neurons
No full text
channel function in rat dorsal vagal neurones
No full text1. Using in situ hybridisation histochemistry in combination with patch-clamp, recordings and specific pharmacological tools, the molecular nature of the channels underlying Ca2+- dependent K+ currents was determined in dorsal vagal neurones (DVNs) of rat brainstem slices. 2. In situ hybridisation analysis at cellular resolution revealed the presence of 'big'-conductance Ca2+- and voltage-activated K+ (BK) channel alpha-subunit mRNA, and of only one 'small' conductance Ca2+-activated K+ (SK) channel subunit transcript, SK3, at very high levels in DVNs. By contrast, SK1 and SK2 mRNAs were below the threshold limit of detection. 3. The SK channel-mediated after-hyperpolarizing current (I-AHP) was blocked by apamin with a half-maximal inhibitory concentration of similar to 2.2 nM. This is consistent with homomultimeric SK3 channels mediating I-AHP in DVNs. I-AHP was also blocked by scyllatoxin (20-30 nM) and curare (100-200 mu M). 4. Application of apamin (100 nM) or scyllatoxin (20 nM) invariably caused a substantial increase to 146.1 +/- 10.4 and 181.8 +/- 12.9% of control, respectively in the spontaneous firing rate of DVNs. Action potential duration was not affected by these SK channel blockers. 5. The selective RK channel blocker iberiotoxin (50 nM) increased action potential duration by 22.5 +/- 7.3%, as did low concentrations of tetraethylammonium (0.5 mM; 99.3 +/- 16.4%) and the Ca2+ channel blocker Cd2+ (100 mu M; 49.5 +/- 20.9%). BK. channel blockade did not significantly affect the firing rate of DVNs. 6. These results allow us to establish a tight correlation between the properties of cloned and native BK and SK channels, and to achieve an understanding, at the molecular level, of their role in regulating the spontaneous firing frequency and in shaping single action potentials of central neurones
- …
