Channelpedia

PubMed 21586701


Referenced in Channelpedia wiki pages of: none

Automatically associated channels: Slo1 , TRP , TRPC , TRPC1 , TRPC3 , TRPC4 , TRPC5 , TRPC6



Title: Role of nonselective cation channels in spontaneous and protein kinase A-stimulated calcium signaling in pituitary cells.

Authors: Melanija Tomic, Marek Kucka, Karla Kretschmannova, Shuo Li, Maria Nesterova, Constantine A Stratakis, Stanko S Stojilkovic

Journal, date & volume: Am. J. Physiol. Endocrinol. Metab., 2011 Aug , 301, E370-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21586701


Abstract
Several receptors linked to the adenylyl cyclase signaling pathway stimulate electrical activity and calcium influx in endocrine pituitary cells, and a role for an unidentified sodium-conducting channel in this process has been proposed. Here we show that forskolin dose-dependently increases cAMP production and facilitates calcium influx in about 30% of rat and mouse pituitary cells at its maximal concentration. The stimulatory effect of forskolin on calcium influx was lost in cells with inhibited PKA (cAMP-dependent protein kinase) and in cells that were haploinsufficient for the main PKA regulatory subunit but was preserved in cells that were also haploinsufficient for the main PKA catalytic subunit. Spontaneous and forskolin-stimulated calcium influx was present in cells with inhibited voltage-gated sodium and hyperpolarization-activated cation channels but not in cells bathed in medium, in which sodium was replaced with organic cations. Consistent with the role of sodium-conducting nonselective cation channels in PKA-stimulated Ca(2+) influx, cAMP induced a slowly developing current with a reversal potential of about 0 mV. Two TRP (transient receptor potential) channel blockers, SKF96365 and 2-APB, as well as flufenamic acid, an inhibitor of nonselective cation channels, also inhibited spontaneous and forskolin-stimulated electrical activity and calcium influx. Quantitative RT-PCR analysis indicated the expression of mRNA transcripts for TRPC1 > TRPC6 > TRPC4 > TRPC5 > TRPC3 in rat pituitary cells. These experiments suggest that in pituitary cells constitutively active cation channels are stimulated further by PKA and contribute to calcium signaling indirectly by controlling the pacemaking depolarization in a sodium-dependent manner and directly by conducting calcium.