Cardiac papillary muscle (n=10) and phrenic nerve- hemidiaphragma (n-16) preparations which differ in receptor type and calcium source have been used to explain the cellular basis of the depressive effect of protamine sulfate on the myocardial contractibility.

These muscle tissues gave diggerent mechanic and electrical responses to 20, 40 and 80 μg/ml concentrations of protamine sulfate. The parameters of the resting membrane potentila (RMP), action potential amplitude (APA) and overshoot (OSH) of cardiac papillary muscle have differed significantly in protamine sulfate concentrations of 40 and 80 μg/ml (p< 0.001). In phrenic nerve-hemidiaphragma preparation, in 40, 80 μg/ml of protamine the RMP changed towards negative values (p < 0.001) dose dependently, the APA values decreased significantly (p < 0.001) with indirect stimulation, and yet in direct stimulation no changes were observed. After 30 minutes of stimulation, and yet in direct stimulation no changes were obsered. After 30 minutes of stimulation, in 55.5 μg/ml verapamil solution, the phrenic nerve-hemidiaphragma preparation's excitability decreased, and yet the contraction force didn't change. Indirect stimulus induced a significant drop of 98.2 percent (p < 0.0001). With direct stimuli,in 20, 40 and 80 μg/ml of protamine, the phrenic nerve-hemidiaphragma preparations didn't exhibit a change in the contraction force, where as indirect stimuli enabled a reduction of 20, 31 and 33 percent respectively (p < 0.05, p > 0.01 and p < 0.01).

In line with our findings, this effect of protamine sulfate seems to be achieved by conformational changes of the ion channels which reduction the ion conduction capacity of the membrane for sodium, potassium, and calcium ions.