Site-specific antibody of (Na(+) + K(+))-ATPase augments cardiac myocyte contraction without inactivating enzyme activity.

(Na(+) + K(+))-ATPase regulates both excitability and contractility of the heart. Little is known about the molecular basis of the enzyme that underlies its cardiac regulatory functions. Here we demonstrate that the (833)KRQPRNPKTDKLVNE(847) region, which resides in the alpha-subunit of rat (Na(+) + K(+))-ATPase, directly participates in the regulation of cardiac contraction. A site-specific antibody (SSA95) against this peptide sequence markedly increased intracellular Ca(2+) transients and contraction (EC(50) = 11.4 nM) in intact rat heart cells without inactivating the (Na(+) + K(+))-ATPase. These novel findings establish the first link between a precise structural region of the (Na(+) + K(+))-ATPase and cardiac positive inotropy.