INT315011

Context Info Confidence 0.57 First Reported 2010 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 1 Total Number 9 Disease Relevance 4.47 Pain Relevance 0.29

transport (Cacna1d) plasma membrane (Cacna1d) transmembrane transport (Cacna1d)

Anatomy Link Frequency neurons 1 cerebellum 1 Cacna1d (Mus musculus)

Pain Link Frequency Relevance Heat Intracerebroventricular 9 78.76 Neurotransmitter 63 76.24 amygdala 9 64.08 long-term potentiation 18 63.44 Hippocampus 9 61.64 Action potential 27 48.76 addiction 27 24.08 Glutamate 36 11.56 anesthesia 9 5.00 adenocard 9 5.00

Disease Link Frequency Relevance Heat Channelopathies 153 100.00 Syndrome 54 98.96 Dystonia 90 98.52 Disease 126 98.48 Malignant Hyperthermia 72 92.44 Anxiety Disorder 18 92.00 Ataxia 18 81.68 Stress 18 76.44 Absence Epilepsy 9 70.88 Targeted Disruption 36 59.12

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Somehow, altered Cav2.1 channel signaling appears to activate pathways that enhance Cav1.2 (but not Cav1.3; [38]) LTCC expression.

Gene_expression (expression) of LTCC

1) Confidence 0.57 Published 2010 Journal Pflugers Arch Section Body Doc Link PMC2883925 Disease Relevance 0.65 Pain Relevance 0.03

The finding that enhanced LTCC expression and most likely activity in Purkinje cells contributes to the paroxysmal dystonia of the tottering phenotype is in good agreement with the observation that dystonic episodes lead to neuronal activation in the cerebellum and its relay nuclei in these mice [9], and that the dystonic phenotype is absent in tottering mice lacking Purkinje cells [11].

Gene_expression (expression) of LTCC in cerebellum associated with dystonia

2) Confidence 0.57 Published 2010 Journal Pflugers Arch Section Body Doc Link PMC2883925 Disease Relevance 0.62 Pain Relevance 0.03

Due to this special role, the question arises whether pathological changes in other (i.e., non-L-type) Ca2+ channel isoforms [14] can lead to secondary changes in LTCC expression and thereby allow them to contribute to disease-related processes.

Gene_expression (expression) of LTCC associated with disease

3) Confidence 0.57 Published 2010 Journal Pflugers Arch Section Body Doc Link PMC2883925 Disease Relevance 0.67 Pain Relevance 0.07

This finding is surprising because LTCC expression in these neurons is very low, thus mediating only about 7% of the total Ca2+ channel current [21, 38].

Gene_expression (expression) of LTCC in neurons

4) Confidence 0.57 Published 2010 Journal Pflugers Arch Section Body Doc Link PMC2883925 Disease Relevance 0.73 Pain Relevance 0.04

Cav1.3 channelopathies (CACNA1D gene)

Gene_expression (gene) of CACNA1D associated with channelopathies

5) Confidence 0.56 Published 2010 Journal Pflugers Arch Section Body Doc Link PMC2883925 Disease Relevance 0.48 Pain Relevance 0

Cav1.3 channelopathies (CACNA1D gene)

Gene_expression (channelopathies) of CACNA1D associated with channelopathies

6) Confidence 0.56 Published 2010 Journal Pflugers Arch Section Body Doc Link PMC2883925 Disease Relevance 0.48 Pain Relevance 0

Obviously, channelopathies in different LTCC ?

Gene_expression (different) of LTCC associated with channelopathies

7) Confidence 0.49 Published 2010 Journal Pflugers Arch Section Body Doc Link PMC2883925 Disease Relevance 0.29 Pain Relevance 0

Transcripts for all four LTCC ?

Gene_expression (four) of LTCC

8) Confidence 0.49 Published 2010 Journal Pflugers Arch Section Body Doc Link PMC2883925 Disease Relevance 0.26 Pain Relevance 0.12

Obviously, channelopathies in different LTCC ?

Gene_expression (channelopathies) of LTCC associated with channelopathies

9) Confidence 0.49 Published 2010 Journal Pflugers Arch Section Body Doc Link PMC2883925 Disease Relevance 0.29 Pain Relevance 0

General Comments

This test has worked.