Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A-type K(+) currents (I(A)) in olfactory receptor neurons have been characterized electrophysiologically but the molecular identities of the underlying channel subunits have not been determined. Using RT-PCR, immunoblot and immunohistochemistry, we found that the two candidate channel families underlying I(A), shaker and shal, are expressed in olfactory epithelia of Swiss Webster mice. Specifically, Kv1.4, the only I(A) candidate from the shaker family, and Kv4.2 and Kv4.3 from the shal family were expressed, but Kv4.1 mRNA was not amplified from the olfactory epithelia. Immunoblot and immunohistochemical studies confirmed the existence of Kv1.4 and Kv4.2/3 subunits. Furthermore, quantitative RT-PCR showed that pituitary adenylate cyclase activating polypeptide (PACAP) reduced the expression of Kv1.4 and Kv4.2 but did not reduce the already low expression of Kv4.3. The PACAP-induced reduction of Kv4.1 and Kv4.2 expression was completely blocked by inhibiting the phospholipase C (PLC) pathway but was still significantly downregulated by PACAP when the cyclic AMP pathway was inhibited. In addition, downstream of the PLC pathway, calcium mediated the reduction of both Kv1.4 and Kv4.2 expression and I(A) current density. Phosphokinase C (PKC) activation did not affect Kv1.4 and Kv4.2 mRNA expression, even though PKC reduced I(A) current density. Together with our previous studies, our data suggest that A-type K(+) currents in olfactory receptor neurons are composed of multiple K(+) channel subunits, among which Kv1.4 and Kv4.2 are subject to transcriptional modulation by PACAP. We also found that PACAP predominately uses a PLC-calcium pathway to modulate Kv4.1 and Kv4.2 expression. Modulation of A-type K(+) current expression may contribute to the previously observed neuroprotective effects of PACAP on olfactory receptor neurons.
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PMID:Pituitary adenylate cyclase activating polypeptide reduces expression of Kv1.4 and Kv4.2 subunits underlying A-type K(+) current in adult mouse olfactory neuroepithelia. 1642 62

Estrogen affects the electrophysiological properties of a number of hypothalamic neurons by modulating K(+) channels via rapid membrane actions and/or changes in gene expression. The interaction between these pathways (membrane vs. transcription) ultimately determines the effects of estrogen on hypothalamic functions. Using suppression subtractive hybridization, we produced a cDNA library of estrogen-regulated, brain-specific guinea pig genes, which included subunits from three prominent K+ channels (KCNQ5, Kir2.4, Kv4.1, and Kvbeta(1)) and signaling molecules that impact channel function including phosphatidylinositol 3-kinase (PI3K), protein kinase Cepsilon (PKCepsilon), cAMP-dependent protein kinase (PKA), A-kinase anchor protein (AKAP), phospholipase C (PLC), and calmodulin. Based on these findings, we dissected the arcuate nucleus from ovariectomized guinea pigs treated with estradiol benzoate (EB) or vehicle and analyzed mRNA expression using quantitative real-time PCR. We found that EB significantly increased the expression of KCNQ5 and Kv4.1 and decreased expression of KCNQ3 and AKAP in the rostral arcuate. In the caudal arcuate, EB increased KCNQ5, Kir2.4, Kv4.1, calmodulin, PKCepsilon, PLCbeta(4), and PI3Kp55gamma expression and decreased Kvbeta(1). The effects of estrogen could be mediated by estrogen receptor-alpha, which we found to be highly expressed in the guinea pig arcuate nucleus and, in particular, proopiomelanocortin neurons. In addition, single-cell RT-PCR analysis revealed that about 50% of proopiomelanocortin and neuropeptide Y neurons expressed KCNQ5, about 40% expressed Kir2.4, and about 60% expressed Kv4.1. Therefore, it is evident that the diverse effects of estrogen on arcuate neurons are mediated in part by regulation of K(+) channel expression, which has the potential to affect profoundly neuronal excitability and homeostatic functions, especially when coupled with the rapid effects of estrogen on K(+) channel function.
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PMID:Estrogen regulation of genes important for K+ channel signaling in the arcuate nucleus. 1759 23