ISSN:
1432-2013
Keywords:
Key words 4-AP
;
Atrioventricular node
;
Flecainide
;
Ito
;
K current
;
Myocyte
;
Quinidine
;
Transient outward current
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract A transient outward current (I to) has been observed in the atrioventricular node (AVN), but its characteristics in Ca-tolerant AVN myocytes have not been investigated previously. In this study, I to was measured from Ca-tolerant rabbit AVN myocytes at 37°C, using the whole-cell patch-clamp technique. With interfering currents inhibited, 500-ms voltage-clamp pulses applied from –80 mV elicited I to at potentials positive to –30 mV, which increased in magnitude with test potential amplitude. This current was completely blocked by external application of 5 mM 4-aminopyridine (4-AP). During a command pulse, I to activated rapidly then inactivated with a bi-exponential time-course. Fast and slow time constants of current inactivation (τf and τs, respectively) showed voltage dependence. At 0 mV, τf was 14.5±2.7 ms and τs was 112.8±21.2 ms, whilst at +60 mV τf was 6.7±1.1 ms and τs was 63.7±9.2 ms (n=25). The steady-state inactivation relationship showed half-maximal inactivation at –33.8 mV (n=8). Re-activation of I to after an inactivating pre-pulse showed a bi-exponential time-course of recovery: τ1 was 196±70 ms, and τ2 was 2707±1010 ms (n=6, at –80 mV). Repetitive application of voltage-clamp test pulses showed that I to inactivation accumulated on repetitive stimulation, but reached a steady state rapidly for a given pulse frequency (0.2–1.0 Hz). AVN I to was sensitive to the class 1 anti-arrhythmic flecainide (EC50 for peak current of 24 µM), which showed selectivity for the rapidly inactivating current component. Quinidine also inhibited I to in a dose-dependent fashion, but did not affect the current time-course. Under voltage-clamp conditions, a simulated diastolic depolarisation from –70 to –45 mV did not significantly reduce I to amplitude, and under current-clamp conditions 4-AP inhibited spontaneous action potentials. Although this is consistent with a significant role for I to in shaping AVN activity, under the conditions of this study 4-AP also partially blocked the ”rapid” delayed rectifier current, I Kr, and so the effects of 4-AP on action potentials could not be attributed exclusively to its effects on I to.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s004240050881
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