PT - JOURNAL ARTICLE AU - Chik, CL AU - Liu, QY AU - Li, B AU - Karpinski, E AU - Ho, AK TI - cGMP inhibits L-type Ca2+ channel currents through protein phosphorylation in rat pinealocytes AID - 10.1523/JNEUROSCI.15-04-03104.1995 DP - 1995 Apr 01 TA - The Journal of Neuroscience PG - 3104--3109 VI - 15 IP - 4 4099 - http://www.jneurosci.org/content/15/4/3104.short 4100 - http://www.jneurosci.org/content/15/4/3104.full SO - J. Neurosci.1995 Apr 01; 15 AB - In this study, the effect of cGMP on the dihydropyridine-sensitive (L- type) Ca2+ current was investigated using the whole cell version of the patch-clamp technique in rat pinealocytes. Dibutyryl-cGMP (1 x 10(-4) M) induced a pronounced inhibition of the L-type Ca2+ channel current. The dibutyryl-cGMP effect was concentration dependent. Elevation of cGMP by nitroprusside had a similar inhibitory action on the L-type Ca2+ channel current. Norepinephrine, which increased cGMP in rat pinealocytes, also inhibited this current. The action of cGMP was independent of cAMP elevation since the cAMP antagonist, Rp-cAMPs, had no effect on the inhibitory action of dibutyryl-cGMP. The involvement of cyclic GMP-dependent protein kinase was suggested by the blocking action of two protein kinase inhibitors, (1-(5-isoquinolinesulfonyl)-2- methylpiperazine (H7) and N-(2-guanidinoethyl)-5- isoquinolinesulfonamide (HA1004), on the dibutyryl-cGMP effect on the L- type Ca2+ channel current. Taken together, these results suggest that (1) cGMP modulates L-type Ca2+ channel currents in rat pinealocytes, causing inhibition of this current; (2) the action of cGMP appears to be independent of cAMP elevation; and (3) phosphorylation by cGMP- dependent protein kinase may be involved.