THE EFFECT OF NICKEL CHLORIDE ON THE ISOLATED HEMIDIAPHRAGM OF THE RAT

1. NiCl2 (cumulative concentrations of 0.56-1.91 mmol l(-1)) produced concentration-dependent depression of tension developed (Td) and the m aximum rate of rise of tension (dT/dt max) of isometric contraction of the isolated rat hemidiaphragm, during direct subtetanic (DST) electr ical stimulation, only. EC(50) values for NiCl2-induced depression of Td and dT/dt max were 0.88 +/- 0.06 and 0.83 +/- 0.13 mmol l(-1), resp ectively. NiCl2 did not significantly change either parameter of the i sometric contraction during direct single-pulse (DSP) electrical stimu lation. 2. Maximal depression of Td and dT/dt max, produced by a singl e concentration of NiCl2 (1 mmol l(-1)) during DST electrical stimulat ion was obtained 20 min after addition of the drug in the bathing medi um. 3. In the normal Tyrode solution, addition of CaCl2 (final concent ration of 5.86 mmol l(-1)) almost completely antagonized the depressan t effect of NiCl2 (1 mmol l(-1)) on Td and dT/dt max during DST electr ical stimulation. In the calcium-free solution, the depression both of Td and dT/dt max produced by NiCl2 (1 mmol l(-1)) was significantly m ore pronounced in comparison with the effect of NiCl2 in the normal Ty rode solution. 4. L-calcium channel activator, Bay K 8644 (25 mu mol l (-1)), significantly potentiated both Td and dT/dt max during DST elec trical stimulation, but NiCl2 (1 mmol l(-1)) decreased both parameters of the isometric contraction even in the presence of this concentrati on of Bay K 8644. On the other hand Bay K 8644 (25 mu mol l(-1)) did n ot antagonize NiCl2-induced depression of Td and dT/dt max. 5. Verapam il (2.5 mu mol l(-1); 45 min of incubation) and lidocaine (0.10 mmol l (-1); 30 min of incubation) significantly potentiated the depression o f Td and dT/dt max, produced by NiCl2 (1 mmol l(-1)), during DST elect rical stimulation. The addition of CaCl2 (final concentration of 7.20 mmol l(-1)) in the bathing medium only partially antagonized the depre ssant synergistic action of both verapamil or lidocaine and NiCl2 on T d and dT/dt max. 6. Forskolin (cumulative concentrations of 2.60-44.20 mu mol l(-1)) fully antagonized NiCl2-induced depression of both Td a nd dT/dt max; propranolol (1 mu mol l(-1)) did not abolish this antago nizing action of forskolin. Also, NiCl2 (cumulative concentrations of 0.56-1.54 mmol l(-1)) did not change potentiating effect of forskolin (23.4 mu mol l(-1)). 7. In conclusion, NiCl2-induced depression of bot h Td and dT/dt max of the isolated rat hemidiaphragm, during DST elect rical stimulation could be specific in part, due to the block of calci um influx, and partially non-specific.