CYCLIC GMP-MEDIATED INHIBITION OF L-TYPE CA2-CELLS( CHANNEL ACTIVITY BY HUMAN NATRIURETIC PEPTIDE IN RABBIT HEART)

1 Effects of atrial natriuretic peptide (ANP) on the L-type Ca2+ chann els were examined in rabbit isolated ventricular cells by use of whole -cell and cell-attached configurations of the patch clamp methods. ANP produced a concentration-dependent decrease (10-100 nM) in amplitude of a basal Ca2+ channel current.2 The inactive ANP (methionine-oxidize d ANP, 30 nM) failed to decrease the current. 3 8-Bromo-cyclic GMP (30 0 mu M), a potent activator of cyclic GMP-dependent protein kinase (PK G), produced the same effects on the basal Ca2+ channel current as tho se produced by ANP. The cyclic GMP-induced inhibition of the Ca2+ chan nel current was still evoked in the presence of 1-isobutyl-3-methyl-xa nthine, an inhibitor of phosphodiesterase. ANP failed to produce inhib ition of the Ca2+ channel current in the presence of 8-bromo-cyclic GM P. 4 In the single channel recording, ANP and 8-bromo-cyclic GMP also inhibited the activities of the L-type Ca2+ channels. Both agents decr eased the open probability (NP0) without affecting the unit amplitude. 5 The present results suggest that ANP inhibits the cardiac L-type Ca 2+ channel activity through the intracellular production of cyclic GMP and then activation of PKG.