Mechanism of anode break stimulation in the heart.
Anodal stimulation is routinely observed in cardiac tissue, but only recently has a mechanism been proposed. The bidomain cardiac tissue model proposes that virtual cathodes induced at sites distant from the electrode 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 whether anodal stimulation has a cellular basis, we measured membrane potential 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 single cells is recruitment of the hyperpolarization-activated inward current 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" current upon release of the hyperpolarization drives the transmembrane potential toward the threshold of sodium channels, initiating an action potential. Time-dependent block of the inward rectifier, I(K1), at hyperpolarized potentials decreases membrane conductance and thereby potentiates the ability of I(f) to depolarize the cell on the break of an anodal pulse. Inclusion of I(f), as well as the block and unblock kinetics of I(K1), in the existing Luo-Rudy action potential model faithfully reproduces anode break stimulation. Thus active cellular properties suffice to explain anode break stimulation in cardiac tissue.
Ranjan
R
R
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Chiamvimonvat
N
N
Thakor
N V
NV
Tomaselli
G F
GF
Marban
E
E
D000200:Action Potentials; D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D004285:Dogs; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D051381:Rats; D011916:Rats, Inbred F344; D011921:Rats, Inbred WKY; D015222:Sodium Channels / Q000378:metabolism
D015222:Sodium Channels