Role of BK Potassium Channels Shaping Action Potentials and the Associated [Ca²⁺]_i Oscillations in GH₃ Rat Anterior Pituitary Cells

Abstract

Measurements of electrical activity and intracellular Ca²⁺ levels were performed in perforated-patch clamped GH₃ cells to determine the contribution of large-conductance calcium-activated K⁺ (BK) channels to action potential repolarization and size of the associated Ca²⁺ oscillations. By examining the dependence of action potential (AP) duration on extracellular Ca²⁺ levels in the presence and the absence of the specific BK channel blocker paxilline, it is observed that plateau-like action potentials are associated to low densities of paxilline-sensitive currents. Extracellular Ca²⁺ increases or paxilline additions are not able to largely modify action potential duration in cells showing a reduced expression of BK currents. Furthermore, specific blockade of these currents with paxilline systematically elongates AP duration, but only under conditions in which short APs and/or prominent BK currents recorded under voltage-clamp mode are present in the same cells. Our data indicate that in GH₃ cells, BK channels act primarily ending the action potential and suggest that by contributing to fine-tuning cellular electrical properties and hence intracellular Ca²⁺ variations, BK channels may play an important role on time- and cell-dependent modulation of physiological outputs in adenohypophyseal cells.

Nitric oxide induces [Ca2+]i oscillations in pituitary GH3 cells: involvement of IDR and ERG K+ currents

“…These two types of K ϩ channels have been observed in GH 3 cells using electrophysiology (8,22,25,37) and RT-PCR (50,51). However, at least under our recording conditions, the contribution of BK channels to I DR seems to be negligible, because CTX and PAX, two specific blockers of these channels, did not reduce the amplitude of these currents and failed to induce [Ca 2ϩ ] i oscillations in quiescent GH 3 cells (data not shown).…”

“…In particular, [Ca 2ϩ ] i oscillations appear to be a result of spontaneous action potentials (16) triggered by the opening of both L-type voltagedependent Ca 2ϩ channels (VDCC) and nonspecific cation channels (45). The ensuing massive influx of Ca 2ϩ ions into the cytoplasm is followed by the activation of Ca 2ϩ -dependent, large-conductance K ϩ (BK) channels (25), which repolarize the cell by cooperating with other K ϩ channels belonging to the family of delayed rectifiers.…”

Cilostazol, an Inhibitor of Type 3 Phosphodiesterase, Stimulates Large-Conductance, Calcium-Activated Potassium Channels in Pituitary GH3Cells and Pheochromocytoma PC12 Cells

“…Recent observations showed that the BK Ca channel activity might play a role in time-and cell-dependent modulation of physiological outputs in anterior pituitary cells (46). The increase of these channel caused by cilostazol might reduce hormonal secretion.…”

Age-related changes in large-conductance calcium-activated potassium channels in mammalian circadian clock neurons

“…A prolonged AP and/or a reduced AHP-as seen in aged SCN neurons and IbTX-treated young SCN neurons-leads to increased [Ca 2+ ] i (Lin et al, 2014;Miranda et al, 2003;Muller et al, 2007;Womack et al, 2009) (Table 1).…”

“…K + current through BK channels accelerates repolarization of the membrane during an action potential (AP); thus, BK current can influence the duration of the AP as well as the afterhyperpolarization (AHP) phase (Cloues and Sather, 2003;Faber and Sah, 2002;Lin et al, 2014;Muller et al, 2007;Shao et al, 1999;Womack and Khodakhah, 2002). Decreased BK currents can change the AP waveform, resulting in a significant increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) (Lin et al, 2014;Miranda et al, 2003;Womack et al, 2009). We therefore asked whether aging alters BK currents in SCN neurons in aged mice, and we asked whether this change affects [Ca 2+ ] i in the SCN, given that [Ca 2+ ] i is elevated in other brain areas in aged animals (Muller et al, 1996;Toescu and Vreugdenhil, 2010).…”