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Hypocalcemia-induced seizure: demystifying the calcium paradox.

Han P, Trinidad BJ, Shi J - ASN Neuro (2015)

Bottom Line: The mechanism of this calcium paradox remains elusive, and very few pathophysiological studies have addressed this conundrum.Nevertheless, several studies primarily addressing other biophysical issues have provided some clues.In this review, we analyze the data of these studies and propose an integrative model to explain this hypocalcemic paradox.

View Article: PubMed Central - PubMed

Affiliation: Barrow Neurological Institute, Dignity Health St Joseph's Hospital and Medical Center and Medical Center, Phoenix, AZ, USA PengCheng.Han@dignityhealth.org.

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Summary of the target ion channels modulated by external calcium. (1) By activating calcium sensing receptors signaling, external calcium reduces sodium influx through Na+ leaky channel , whereas low calcium enhances sodium influx; (2) high external calcium reduces sodium influx through voltage-gated sodium channels, whereas low external calcium enhances sodium influx through a proposed “surface charge” mechanism; (3) high external calcium enhances potassium outflow, whereas low external calcium reduces potassium outflow; (4) high external calcium reduces cation influx, whereas low external calcium enhances cation influx through cyclic nucleotide-gated ion channels; (5) high external calcium reduces ion influx through AMPA receptors, whereas low external calcium enhances it; (6) by activating calcium sensing receptors, external calcium inhibits glutamate release, whereas low external calcium enhances it.
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fig2-1759091415578050: Summary of the target ion channels modulated by external calcium. (1) By activating calcium sensing receptors signaling, external calcium reduces sodium influx through Na+ leaky channel , whereas low calcium enhances sodium influx; (2) high external calcium reduces sodium influx through voltage-gated sodium channels, whereas low external calcium enhances sodium influx through a proposed “surface charge” mechanism; (3) high external calcium enhances potassium outflow, whereas low external calcium reduces potassium outflow; (4) high external calcium reduces cation influx, whereas low external calcium enhances cation influx through cyclic nucleotide-gated ion channels; (5) high external calcium reduces ion influx through AMPA receptors, whereas low external calcium enhances it; (6) by activating calcium sensing receptors, external calcium inhibits glutamate release, whereas low external calcium enhances it.

Mentions: The inverse relationship between extracellular calcium and neuronal excitability could be explained by several complementary molecular events (summarized in Table 1 and Figure 2). External calcium inhibits NALCNs, shifts the voltage dependency of voltage-gated Na+ channels, stabilizes CNG channels, reduces inward current through AMPA channels, and depresses the release of excitatory neurotransmitters. Conversely, it enhances transient K+ current and KCa channels and perhaps potentiates GABA sensitivity. Some of these modulatory effects may depend on CaSR while others may require calcium influx. It is these processes that we theorize may help shed light on the calcium paradox and lead to further understanding of the mechanisms behind production of seizures through hypocalcemia.Figure 2.


Hypocalcemia-induced seizure: demystifying the calcium paradox.

Han P, Trinidad BJ, Shi J - ASN Neuro (2015)

Summary of the target ion channels modulated by external calcium. (1) By activating calcium sensing receptors signaling, external calcium reduces sodium influx through Na+ leaky channel , whereas low calcium enhances sodium influx; (2) high external calcium reduces sodium influx through voltage-gated sodium channels, whereas low external calcium enhances sodium influx through a proposed “surface charge” mechanism; (3) high external calcium enhances potassium outflow, whereas low external calcium reduces potassium outflow; (4) high external calcium reduces cation influx, whereas low external calcium enhances cation influx through cyclic nucleotide-gated ion channels; (5) high external calcium reduces ion influx through AMPA receptors, whereas low external calcium enhances it; (6) by activating calcium sensing receptors, external calcium inhibits glutamate release, whereas low external calcium enhances it.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2 - License 3
Show All Figures
getmorefigures.php?uid=PMC4374060&req=5

fig2-1759091415578050: Summary of the target ion channels modulated by external calcium. (1) By activating calcium sensing receptors signaling, external calcium reduces sodium influx through Na+ leaky channel , whereas low calcium enhances sodium influx; (2) high external calcium reduces sodium influx through voltage-gated sodium channels, whereas low external calcium enhances sodium influx through a proposed “surface charge” mechanism; (3) high external calcium enhances potassium outflow, whereas low external calcium reduces potassium outflow; (4) high external calcium reduces cation influx, whereas low external calcium enhances cation influx through cyclic nucleotide-gated ion channels; (5) high external calcium reduces ion influx through AMPA receptors, whereas low external calcium enhances it; (6) by activating calcium sensing receptors, external calcium inhibits glutamate release, whereas low external calcium enhances it.
Mentions: The inverse relationship between extracellular calcium and neuronal excitability could be explained by several complementary molecular events (summarized in Table 1 and Figure 2). External calcium inhibits NALCNs, shifts the voltage dependency of voltage-gated Na+ channels, stabilizes CNG channels, reduces inward current through AMPA channels, and depresses the release of excitatory neurotransmitters. Conversely, it enhances transient K+ current and KCa channels and perhaps potentiates GABA sensitivity. Some of these modulatory effects may depend on CaSR while others may require calcium influx. It is these processes that we theorize may help shed light on the calcium paradox and lead to further understanding of the mechanisms behind production of seizures through hypocalcemia.Figure 2.

Bottom Line: The mechanism of this calcium paradox remains elusive, and very few pathophysiological studies have addressed this conundrum.Nevertheless, several studies primarily addressing other biophysical issues have provided some clues.In this review, we analyze the data of these studies and propose an integrative model to explain this hypocalcemic paradox.

View Article: PubMed Central - PubMed

Affiliation: Barrow Neurological Institute, Dignity Health St Joseph's Hospital and Medical Center and Medical Center, Phoenix, AZ, USA PengCheng.Han@dignityhealth.org.

Show MeSH
Related in: MedlinePlus