STUDIES ON VERATRUM ALKALOIDS. XXV. VERATRINE RESPONSE AND ANTIVERATRINIC ACTION IN FROG SARTORIUS MUSCLE

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

Simultaneous records were made of the isometric tension developed by about 100 fibers of the frog sartorius muscle and the electrical activity of a single fiber.

Administration of veratridine 10^-7 resulted in a state of the muscle where a single stimulus was followed by the characteristic two-peaked tension response simultaneous with a series of electrical discharges; these were superimposed on a negative afterpotential. The second tension rise (VR) and the frequency of firing was higher (7.2 maec. average distance) when the muscle had been allowed to rest for four minutes instead of for only one minute (19.5 msec. average distance). The membrane potential under veratridine was found relatively low (73.9 mV) and unstable, the action potential without an overshoot (47.2 mV).

Addition of veratramine 10^-5, strophanthin 3 10^-6, quinine or quinidine 10^-5 to the veratrinized muscle normalized the situation in that a single stimulus was again followed by a single action potential and twitch. In the transient period when the full antiveratrinic action had not yet developed, unusually slow repetitive discharges were observed together with a small second tension rise.

At lower temperatures (6°C.) higher veratridine concentrations (1.3 10^-6) were necessary to elicit a VR, but the antiveratrinic action of veratramine was at all temperatures fully developed at 10^-5.

Lack of oxygen, addition of sodium cyanide, iodoacetic acid, and dinitrophenol reduced the amplitude of both parts of the mechanical response simultaneously; they had no antiveratrinic action.

Sodium excess in the Ringer bath diminished the twitch before it influenced the VR.

Like curare, decamethonium did not affect the VR and repetitive discharges in a concentration which blocked neuromuscular transmission.

A mechanism influencing the ionic flux into and out of the muscle cell in connection with excitation is discussed as a possible site of action of veratridine.