Depolarization by high intracellular potassium triggers calcium channel opening.
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CONTESTED
contested - evenly split
refutedsupported
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4 sources for · 1 against
While standard physiological models describe membrane depolarization via potassium accumulation or conductance changes as a trigger for opening voltage-gated calcium channels, specific experimental studies report conflicting results, such as depolarization failing to elicit calcium influx in certain cell types like developing myoblasts.
Chick myoblast fusion in culture was investigated using prostanoid synthesis inhibitors to delay spontaneous fusion. During this delay myoblast fusion could be induced by prostaglandin E1 (PGE1), by raising extracellular potassium and by addition of carbachol. Carbachol-induced fusion, but not PGE-induced fusion, was prevented by the acetylcholine receptor blocker alpha-bungarotoxin. Fusion induced by any of these agents was prevented by the Ca channel blockers lanthanum and D600. The threshold for potassium-induced fusion was 7-8 mM; maximal fusion occurred at 16-20 mM. Low extracellular potassium inhibited spontaneous fusion. Intracellular potassium in fusion competent myoblasts was 101 m-moles/l cell. Calcium flux measurements demonstrated that high potassium increased calcium permeability in fusion-competent myoblasts. A 30-s exposure to high potassium or PGE1 was sufficient to initiate myoblast fusion. Anion-exchange inhibitors (SITS and DIDS) delayed spontaneous myoblast fusion and blocked fusion induced by PGE1 but not carbachol. Blocking the acetylcholine receptor shifted the dose-response relation for PGE-induced fusion to higher concentrations. PGE1-induced fusion required chloride ions; carbachol-induced fusion required sodium ions. Provided calcium channels were available, potassium always induced fusion. We conclude that myoblasts possess at least three, independent pathways, each of which can initiate myoblast fusion and that the PGE-activated pathway and the ac
Ca(2+) influx appears to be important for triggering myoblast fusion. It remains, however, unclear how Ca(2+) influx rises prior to myoblast fusion. The present study examines a possible involvement of the voltage-dependent Ca(2+) influx pathways. Treatment with the L-type Ca(2+) channel blockers, diltiazem, and nifedipine did not alter cytosolic Ca(2+) levels. Depolarization with high K(+) solution and activation of Ca(2+) channel with Bay K 8644, and agonist of voltage dependent Ca(2+) channels, failed to elicit increases intracellular Ca(2+) level, indicating the absence of depolarization-operated mechanisms. In contrast, phloretin, an agonist of Ca(2+)-activated potassium (K(Ca)) channels, was able to hyperpolarize membrane potential and promoted Ca(2+) influx. These effects were completely abolished by treatment of charybdotoxin, a specific inhibitor of K(Ca) channels. In addition, gadolinium, a potent stretch-activated channel (SAC) blocker, prevented the phloretin-mediated Ca(2+) increase, indicating the involvement of SACs in Ca(2+) influx. Furthermore, phloretin stimulated precocious myoblast fusion and this effect was blocked with gadolinium or charybdotoxin. Taken together, these results suggest that induced hyperpolarization, but not depolarization increases Ca(2+) influx through stretch-activated channels, and in turn triggers myoblast fusion.
Contraction in vascular smooth muscle (VSM) is generally initiated by the membrane excitation that triggers an increase in cytoplasmic free Ca2+ ([Ca2+]i) which then activates the contractile apparatus (19, 26). In general, [Ca2+]i can be increased by i) Ca2+ influx, through voltage-gated Ca2+ channels by depolarization of the plasma membrane, and/or through receptor-operated Ca2+ channels by vasoconstrictive mediators; ii) Ca2+ release from sarcoplasmic reticulum (SR), mitochondrial, and other intracellular Ca2+ stores; iii) decreased Ca2+ extrusion (via Na-Ca exchange, Ca2+-ATPase) and sequestration (via mitochondria, SR, Ca2+-binding proteins); and iv) increased Ca2+ entry via Na-Ca exchange. Ca2+ influx through voltage-gated Ca2+ channels is controlled mainly by the membrane potential (Em) (35) that is dominated by K+ channel permeability and the transmembrane K+ distribution (14). The smooth muscle cell membrane possesses a high membrane input resistance (13, 35, 56); thus, a small decrease in K+ conductance should cause a relatively large depolarization, which should, in turn, open voltage-gated Ca2+ channels and thereby increase [Ca2+]i.
The bag cell neurons of Aplysia provide a model system in which to investigate the effects of hyperosmolality on the electrical and secretory properties of neurons. Brief stimulation of these neurons triggers an afterdischarge of action potentials that lasts approximately 20-30 min, during which time they release several neuroactive peptides. We have found that pre-incubation of intact clusters of bag cell neurons in hyperosmotic media prior to stimulation prevents the initiation of afterdischarges. Furthermore, an increase in osmolality of the external medium during an ongoing afterdischarge causes its premature termination. Hyperosmotic media attenuate the release of peptide evoked by both electrically stimulated afterdischarges and potassium-induced depolarization. The ability of high potassium to depolarize the bag cell neurons is, however, not impaired. Exposure of isolated bag cell neurons to hyperosmotic media also inhibits the amplitude of action potentials evoked by depolarizing current injection and attenuates the voltage-dependent calcium current. In isolated bag cell neurons loaded with the calcium indicator dye, fura-2, hyperosmotic media reduced the rise in intracellular calcium levels that normally occurs in response to depolarization. Our results suggest that the effects of hyperosmotic media on peptide secretion in bag cell neurons can largely be attributed to their effects on calcium entry.
Abstract The zona glomerulosa (ZG) of the adrenal cortex regulates blood pressure and electrolyte homeostasis through aldosterone production. In ZG cells, the serum concentrations of potassium and angiotensin II (Ang II) trigger calcium oscillations that drive aldosterone synthesis. Changes in serum osmolality also modulate aldosterone production in a chloride-dependent fashion, but the involved proteins remain unclear. Because the chloride channel ClC-2 is activated by hypoosmolality, we investigated its role in ZG osmoregulation using ClC-2 knockout (KO) mice. Intracellular chloride concentrations in the ZG are high, and opening of ClC-2 leads to chloride efflux, depolarization and voltage-dependent calcium influx. Under hypoosmolar conditions, intracellular chloride levels were higher in ClC-2 KO ZG cells than in the WT, suggesting that hypoosmolality triggers chloride efflux via ClC-2 in the WT, and that this efflux is absent in the KO. WT cells responded to hypoosmolality with an increase in intracellular calcium levels, likely mediated by chloride efflux and depolarization. This response was again abrogated in the KO, despite faster calcium spiking. In line with increased intracellular calcium levels, WT adrenal slices upregulated aldosterone production upon hypoosmolar treatment in vitro, whereas aldosterone production remained unchanged in the KO. These findings establish a role for ClC-2 in the ZG’s response to reductions in extracellular osmolality through the outfl
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