cGMP Inhibits L-Type Ca2+ channel currents through protein phosphorylation in rat pinealocytes

Abstract

In this study, the effect of cGMP on the dihydropyridinesensitive (L-type) Ca2+ current was investigated using the whole cell version of the patch-clamp technique in rat pinealocytes. Dibutyryl-cGMP (1 × 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.