Kanamycin as a Ca++ Antagonist

ABSTRACT

In order to elucidate mechanisms of Ca++ antagonistic action of kanamycin in the biological system, the effects of kanamycin on Ca++ transport in sarcoplasmic reticulum of rabbit skeletal muscle and liver mitochondria were studied. At the same time, the effect of the agent on Bowditch and Woodworth phenomena of rabbit heart as well as the superprecipitation of actomyosin isolated from rabbit skeletal muscle were studied. Since kanamycin inhibits the Bowditch staircase phenomena in rabbit cardiac muscle, it is speculated that kanamycin inhibits Ca++ influx across the cell membrane which is required for the muscular contraction. Kanamycin also inhibits the Woodworth staircase phenomena, indicating a decrease in size of the Ca++ pool in cardiac muscle which may be brought about by an inhibition of Ca++ transport in sarcoplasmic reticulum and mitochondria. Actually, kanamycin was found to inhibit both the activities of Ca++ activated adenosine triphosphatases (ATPase) and Ca++ transport in sarcoplasmic reticulum and mitochondria. Kanamycin also inhibits both the development of superprecipitation and the activity of Ca++activated ATPase of skeletal actomyosin in rabbits. From the results obtained above, it may be concluded that kanamycin possesses a Ca++ antagonistic action in the biological system.