RELATIONSHIP BETWEEN DECREASED FUNCTION AND O-2 CONSUMPTION CAUSED BYCYCLIC-GMP IN CARDIAC MYOCYTES AND L-TYPE CALCIUM CHANNELS

We tested the hypothesis that part of the decreased function and metab olism caused by cyclic guanosine monophosphate (GMP) in beating cardia c myocytes is related to inhibition of L-type calcium channels. The st eady state oxygen consumption (VO2) of a suspension of ventricular myo cytes isolated from hearts of New Zealand white rabbits was measured u sing oxygen electrodes. Cellular cyclic GMP levels were determined by radioimmunoassay. Cell shortening was measured with a video edge detec tor. The VO2 was obtained after: (1) adding sodium nitroprusside (NP 1 0(-8,-6,-4) M), (2) pretreatment by BAY K8644 10(-5) M (BAY, L-type ca lcium channel activator), nifedipine 10(-4) M (NF, L-type calcium chan nel blocker) or forskolin 10(-7) M (FK, adenylate cyclase activator), then adding NP10(-8,-6,-4) M, (3) pretreatment with both FK 10(-7) M a nd NF 10(-4) M and subsequently adding NP 10(-8,-6,-4) M. NP 10(-4) M decreased VO2 from 707 +/- 34 to 410 +/- 13 (nl O-2/min per 10(5) myoc ytes), decreased the percentage of shortening (Pcs) from 5.7 +/- 0.6 t o 3.7 +/- 0.5 and the rate of shortening (Rs) from 65.5 +/- 4.5 (mu m/ s) to 46.2 +/- 5.5. NP 10(-4) M also increased cyclic GMP from 264 +/- 70 (fmol/10(5) myocytes) to 760 +/- 283. Both BAY and FK increased VO 2, Pcs and Rs without changing cyclic GMP. NF decreased Pcs, Rs and VO 2. Similar metabolic and functional effects of NP were observed with p retreatment with these agents separately, compared to NP alone, and th e elevation of cyclic GMP level was not different from the control gro up. With FK alone, NP 10(-4) M decreased VO2 by 51%, Pcs by 44% and Rs by 39%. In the presence of both FK and NF, the negative effects of NP were diminished significantly. NP 10(-4) M decreased VO2 by 37%, Pcs by 25% and Rs 20%. Thus, in beating cardiac myocytes, the negative met abolic and functional effects of cyclic GMP were related to inhibition on L-type calcium channels only when adenylate cyclase was stimulated .