Mechanism of anode break stimulation in the heart

Ravi Ranian, Nipavan Chiamvimonvat, Nitish V. Thakor, Gordon F. Tomaselli, Eduardo Marban

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1850-1863
Number of pages14
JournalBiophysical Journal
Volume74
Issue number4
StatePublished - Jan 1 1998
Externally publishedYes

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Electrodes
Membrane Potentials
Action Potentials
Sodium Channels
Muscle Cells
Pulse
Canidae
Tail
Guinea Pigs
Membranes

ASJC Scopus subject areas

  • Biophysics

Cite this

Ranian, R., Chiamvimonvat, N., Thakor, N. V., Tomaselli, G. F., & Marban, E. (1998). Mechanism of anode break stimulation in the heart. Biophysical Journal, 74(4), 1850-1863.

Mechanism of anode break stimulation in the heart. / Ranian, Ravi; Chiamvimonvat, Nipavan; Thakor, Nitish V.; Tomaselli, Gordon F.; Marban, Eduardo.

In: Biophysical Journal, Vol. 74, No. 4, 01.01.1998, p. 1850-1863.

Research output: Contribution to journalArticle

Ranian, R, Chiamvimonvat, N, Thakor, NV, Tomaselli, GF & Marban, E 1998, 'Mechanism of anode break stimulation in the heart', Biophysical Journal, vol. 74, no. 4, pp. 1850-1863.
Ranian R, Chiamvimonvat N, Thakor NV, Tomaselli GF, Marban E. Mechanism of anode break stimulation in the heart. Biophysical Journal. 1998 Jan 1;74(4):1850-1863.
Ranian, Ravi ; Chiamvimonvat, Nipavan ; Thakor, Nitish V. ; Tomaselli, Gordon F. ; Marban, Eduardo. / Mechanism of anode break stimulation in the heart. In: Biophysical Journal. 1998 ; Vol. 74, No. 4. pp. 1850-1863.
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