Effect of pH and Electrostatic Interactions on Myofilament Lattice Volume

Abstract

Changes interfilament lattice spacing is a major determinant of force production in striated muscle with reductions in force generation being observed with both expansion and compression of the lattice spacing relative to the normal physiological values. Previous studies have concluded that lattice spacing depends complexly on the balance of outward repulsive forces and inward attractive and compressive forces between thick and thin filaments. Since lattice spacing has important implications on force generation, we examined the effects of alterations in filament charge, induced by changes in intracellular pH (by the rapid application and withdrawal of 30 mM NH4Cl), on lattice spacing in intact twitching cardiac trabeculae. Since we observed changes in sarcomere length in response to changes in intracellular pH and since changes in sarcomere length induce changes in lattice spacing as a result of the isovolumic volume behavior of intact sarcomeres, sarcomere length was maintained at a fixed value (∼2.2 μm) during the pH interventions. Lattice spacing increased (p < 0.05) following NH4Cl wash in (measured after 5 minutes) when the pH is estimated to increase to ∼7.8 (Balnave 2000 J. Physiol.) to 36.9 +/-0.2. Following the washout of NH4Cl (which is estimated to decrease pH to ∼6.5 (Swietach 2005 J. Physiol.)) lattice spacing increased to 37.6+/−0.4 elevated above (P < 0.05) the space observed at control pH. Since the isoelectric point for myofilaments is ∼5 (Naylor, Biophys J, 1985), our findings suggest that, in addition to electrostatic, van der Waals' and osmotic forces, other pH-sensitive forces are also critical determinants of the lattice spacing, possibly the M-protein, myomesin or other M-line proteins which are postulated to hold thick filaments together in the M-band of striated muscle.