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.

Electrophysiological and morphological properties of neurons in the prepositus hypoglossi nucleus that express both ChAT and VGAT in a double‐transgenic rat model

“…Our previous studies demonstrated that a majority of PHN neurons fire spontaneously, whereas some PHN neurons exhibit SMOCs (Saito & Yanagawa, ; Zhang et al ., ); these outward currents display slower kinetics compared with the postsynaptic currents and are induced by Ca 2+ ‐activated K + channels, which are activated by Ca 2+ ‐induced Ca 2+ release from the endoplasmic reticulum via ryanodine receptors (Arima et al ., ; Cui et al ., ; Klement et al ., ; Saito & Yanagawa, ). In the present study, most D+ neurons (67/70) exhibited spontaneous firing (Fig.…”

International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels

“…Neurotransmitter receptors that also elevate cytoplasmic Ca 2+ levels, either by Ca 2+ influx through the receptor as in the case of NMDA receptors (Oliver et al, 2000;Faber et al, 2005;Ngo-Anh et al, 2005), or by triggering release of Ca 2+ from intracellular stores (Power and Sah, 2008;Klement et al, 2010), can also produce neuronal hyperpolarization by activating K Ca 2 channels. The trafficking of K Ca 2.2 channel subunits into and out of the spines on the dendrites of hippocampal neurons determines the onset and amplitude of longterm potentiation, a prolonged increase in excitatory synaptic transmission that follows repetitive synaptic stimulation of hippocampal pyramidal cells (Lin et al, 2008;Allen et al, 2011).…”

Understanding calcium waves and sparks in central neurons

“…These currents result from the activation of BK channels and lead to muscle relaxation. In a few neurons, similar currents called spontaneous miniature outward currents (SMOCs) have been detected that activate either SK channels (in rat medial preoptic neurons 129 ) or BK channels (in parasympathetic cardiac neurons 130 ). These studies did not determine in which part of the neuron the currents were activated nor did they suggest a clear consequence of their generation.…”