DIMINISHED MYOFIBRILLAR SENSITIVITY TO CALCIUM PRODUCED BY SIMULTANEOUS SUPERFUSION OF CAMP AND PHOSPHODIESTERASES INHIBITORS IN TOAD (BUFO-ARENARUM-HENSEL) VENTRICLE

Experiments were performed in EGTA-skinned trabeculae from toad ventri cle to explore the effects of the cAMP on calcium sensitivity of the c ontractile system. 10(-3) M of the cAMP derivative dibutyryl cAMP (dcA MP) failed to affect calcium sensitivity of chemically skinned ventric ular trabeculae. 10(-5) M of the phosphodiesterase inhibitor isobutylm ethylxantine (IBMX) produced a significant shift to the left of the te nsion-pCa relationship. The computed half maximally activating pCa (pC a50) were 6.32 +/- 0.03 and 6.40 +/- 0.01 in the absence and presence of IBMX respectively, (P<0.05). Simultaneous perfusion of 10(-5) M IBM X and 10(-3) M dcAMP suppressed the leftward shift of the tension-pCa curve induced by IBMX (pCa50 : 6.33 +/- 0.04 and 6.33 +/- 0.05 for con trol and IBMX respectively). Perfusion with the phosphodiesterase inhi bitor milrinone (10(-5) M), did not produce any significant changes in the tension-pCa relationship. Simultaneous perfusion of 10(-5) M milr inone and 10(-3) M dcAMP significantly shifted to the right the tensio n-pCa curve. The computed pCa50 were 6.32 +/- 0.02 and 6.23 +/- 0.03 u nder control conditions and in the presence of dcAMP plus milrinone re spectively (P < 0.05). In agreement with what has been described in ma mmalian heart, the results indicate that in amphibian ventricle, cAMP produced a decrease in the calcium sensitivity of the contractile prot eins that is only evident in the presence of phosphodiesterase inhibit ors. It is suggested that this decrease in myofilament sensitivity to calcium may be one of the mechanisms by which beta-agonists enhance my ocardial relaxation in the amphibian heart.