MECHANISM OF ANODE BREAK STIMULATION IN THE HEART

Anodal stimulation is routinely observed in cardiac tissue, but only r ecently has a mechanism been proposed. The bidomain cardiac tissue mod el proposes that virtual cathodes induced at sites distant from the el ectrode initiate the depolarization. In contrast, none of the existing cardiac action potential models (Luo-Rudy phase I and II, or Oxsoft) predict anodal stimulation at the single-cell level. To determine whet her anodal stimulation has a cellular basis, we measured membrane pote ntial and membrane current in mammalian ventricular myocytes by using whole-cell patch clamp. Anode break responses can be readily elicited in single ventricular cells. The basis of this anodal stimulation in s ingle cells is recruitment of the hyperpolarization-activated inward c urrent I-f. The threshold of activation for I-f is -80 mV in rat cells and -120 mV in guinea pig or canine cells. Persistent I-f ''tail'' cu rrent upon release of the hyperpolarization drives the transmembrane p otential toward the threshold of sodium channels, initiating an action potential. Time-dependent block of the inward rectifier, I-K1, at hyp erpolarized potentials decreases membrane conductance and thereby pote ntiates the ability of I-f to depolarize the cell on the break of an a nodal pulse. Inclusion of I-f, as well as the block and unblock kineti cs of I-K1, in the existing Luo-Rudy action potential model faithfully reproduces anode break stimulation. Thus active cellular properties s uffice to explain anode break stimulation in cardiac tissue.