INHIBITORY INFLUENCE OF PHOSPHATE AND ARSENATE ON CONTRACTION OF SKINNED SKELETAL AND CARDIAC-MUSCLE

It has been widely observed that P(i) decreases maximum calcium-activated force (F(max)) and calcium sensitivity of skinned skeletal and cardiac muscle. However, whether a particular ionic species of P(i) (i.e., H2PO4-) is responsible for these effects is controversial. To clarify this issue, we examined the influence of P(i) and its structural analogue arsenate (As(i)) on contraction of skinned rabbit psoas (fast twich), soleus (slow twitch), and cardiac papillary muscle. As(i) decreased F(max) of all three muscle types to a greater extent than P(i). Both P(i) and As(i) decreased calcium sensitivity of psoas and cardiac muscles, with As(i) having the greater effect. The effect of the protonated form of P(i) and As(i) on F(max) was evaluated by measuring the response to 30 mM total P(i) or As(i) at pH 7.4, 7.0, 6.6, and 6.2. In psoas fibers we found that both P(i) and As(i) were more effective in decreasing F(max) as the pH was lowered (i.e., as the concentration of the diprotonated forms increased). On the contrary, soleus and cardiac fibers did not exhibit this behavior. These differences in the effects of P(i) and As(i) on F(max) in psoas vs. cardiac and soleus muscles may be related to differences in their myosin heavy chains other than the binding site for the gamma-phosphate of ATP which appears to be conserved for all myosins.