J. Kobayashi, H. Nakamura, Y. Hirata and Y. Ohizumi. Effect of venoms from Conidae on skeletal, cardiac and smooth muscles. Toxicon 20, 823–830, 1982.—The effects of the venoms of 29 species of Conidae were studied on the mouse isolated diaphragm, the guinea-pig isolated left atria and ileum, and the rabbit isolated aorta. When the directly stimulated mouse diaphragm was exposed to the venom (10 −4 g/ml) of C. geographus, there occurred a marked decline in twitch tension. The venoms of C. magus (3 × 10 −6 g/ml) and C. striatus (10 −3 g/ml) also caused complete loss of contractile response to electrical stimulation. This was followed by a gradual rise in the baseline. The venoms (10 −6−3 × 10 −5 g/ml) of C. magus and C. striatus caused dose-dependent increases in the contractile force of the electrically driven guinea-pig left atria. The venoms (10 −5−10 −4 g/ml) of C. eburneus and C. tessulatus also elicited long-lasting positive inotropic actions on the atria. The inotropic actions induced by the venoms of C. magus and C. striatus were abolished by tetrodotoxin (TTX, 10 −6 M), but were not affected by verapamil (3 × 10 −7 M), whereas those induced by the venoms of C. eburneus and C. tessulatus were completely inhibited by verapamil (3 × 10 −7 M), but were not modified by TTX (10 −6 M). These results suggest that the inotropic actions of the venoms of C. magus and C. striatus may be due to an increase in Na + permeability of the cardiac cell membrane, while those of venoms of C. eburneus and C. tessulatus may be due to an increase in Ca 2+ permeability. The venoms (10 −6 g/ml) of C. magus and C. striatus elicited rhythmic, transient contractions of the guinea-pig ileum followed by relaxations, which were blocked by TTX (10 −6 M). This suggests that these biphasic responses were caused by increasing Na + permeability of the nerve cell membrane. On the other hand, the venoms (10 −4 g/ml) of C. eburneus and C. tessulatus caused transient contractions of the ileum followed by relaxations. The venoms (10 −4 g/ml) of C. tessulatus and C. eburneus caused marked, long-lasting contractions of the rabbit aorta which were abolished by verapamil (10 −6 M), but were not affected by TTX (5 × 10 −7 M) or phentolamine (10 −6 M). It is suggested that these venoms increase the verapamil-sensitive Ca 2+ influx across the smooth muscle membrane of the aorta, resulting in contractions. The active principles in the venoms of C. geographus, C. textile and C. imperialis were stable at 100°C for 15 min and passed through PM 10 filters, suggesting molecular weights lower than 10,000. On the other hand, the active principles in the venoms of C. magus, C. striatus, C. tessulatus and C. eburneus were partially destroyed with heating and were kept in the retentate of the PM 10 filters.