TWITCH POTENTIATION, CONTRACTURES AND ALTERATIONS IN CALCIUM FLUXES PRODUCED BY TETRAALKYLAMMONIUM IONS

¹ Department of Pharmacology, Schools of Medicine and Dental Medicine, University of Connecticut, McCook Hospital, Hartford, Connecticut

Potentiation by tetrabutylammonium ions (TBA) of the twitch response of frog sartorius muscles is delayed in onset and depends on the frequency of stimulation. Progressively greater twitch tension occurs during trains of repetitive stimulation at rates of 0.1 or 0.5 Hz. Decay of twitch potentiation also occurs when an appropriate rest period is interposed between trains of stimulation. Tetrapropylammonium ions fail to cause twitch potentiation. Twitch potentiation by tetraethylammonium ions is rapid in onset and does not vary with frequency of stimulation. Action potentials recorded from sartorius muscle fibers treated with TBA show marked and progressive increases in duration during trains of stimulation at 0.1 or 0.5 Hz. The frequency-dependent twitch potentiation and prolongation of the action potential by TBA are probably related events. Muscles bathed in 9 mM Ca Ringer's solution undergo contracture when treated with TBA. The contractures are delayed in onset (3-5 minutes), attain maximum in 15 to 20 minutes and decline to resting tension in about 45 minutes. The TBA-induced contractures occur in muscles treated with tetrodotoxin, sodium-free solutions and hypertonic solutions. TBA does not cause contractures of muscles treated with 10 mM KC1 Ringer's solution. Tetrapropylammonium ions cause contractures similar to those caused by TBA in about half of the muscles studied. Calcium uptake (⁶⁵Ca or ⁸⁵Sr) was enhanced by TBA by a process that, in turn, was blocked by elevated concentrations of potassium (7.5-10.0 mM). By contrast, calcium efflux was depressed by both tetrapropylammonium ions and TBA in standard and in 10 mM KC1 Ringer's solution. It is concluded that contractures caused by TBA are due to increased uptake of calcium from the extracellular fluid and a corresponding increase in the sarcoplasmic calcium content.