Evidence suggesting time-dependent recovery of excitability in the in vivo human sinus node

Abstract

The sinus node (SN) possesses the properties of automaticity and conduction. Automaticity arises in its dominant and latent pacemaker cells and results from both time and voltage-dependent ionic currents as shown by in vitro studies. 1,2 Conduction is required for propagation of the generated impulse. Both automaticity and conduction can be assessed in vivo by way of clinical electrophysiologic studies, as well as in vitro. 3,4 The SN also displays excitability; i.e., the ability for an action potential to be produced by an applied stimulatory current. 1,2 In the SN, in vitro studies have shown that the recovery of excitability, the ability of a cell to be reexcited by a subsequent application of current, is also both voltage-dependent, typical of all cardiac tissues, and time-dependent, characteristic of only “slow response” fibers. 1,2 Time-dependent recovery outlasts voltage-dependent recovery; thus, SN cells cannot be reexcited by a stimulatory current (are “refractory”) despite a return of membrane potential to baseline voltage until time-dependent recovery has also been achieved. 1,2 Unlike automaticity and conduction, recovery of SN excitability has not been directly studied in humans since clinical electrophysiologic studies have not encompassed the ability to directly stimulate the SN and verify such stimulation. Nevertheless, one might expect that similar mechanisms would be operative in vivo as in vitro. In the 1980s, 2 developments occurred which bear on the ability to assess excitability in vivo. The first was the recognition and verification that SN refractoriness could be studied through retrograde activation 5–8 (i.e., the responses to atrial premature stimuli can be analyzed to determine the coupling interval at which retrograde penetration of the SN is lost and the complexes become interpolated). Interpolation has been shown to occur when SN refractoriness is encountered. 5 The second was the development of SN electrography 9–12 and the documentation that the extracellular, transcatheter SN electrogram truly reflects the action potentials occurring in the underlying SN. We believe these 2 developments could be combined to indicate whether time-dependent recovery of SN excitability exists in vivo. If SN refractoriness outlasts the voltage excursions of the SN depolarization on the SN electrogram, time dependence of recovery of excitability is suggested.