Article date: September 2002
By: Wei‐Guang Ding, Futoshi Toyoda, Hiroshi Matsuura in Volume 137, Issue 2, pages 253-262
In guinea‐pig sino‐atrial (SA) node cells the delayed rectifier K+ current (IK) is composed of rapidly and slowly activating components of IK (IKr and IKs, respectively). The present study was undertaken to characterize the blocking action of the chromanol derivative 293B on IKs in guinea‐pig SA node cells using whole‐cell patch‐clamp technique.
Bath application of 293B blocked IKs, elicited by 4‐s depolarizing voltage pulses from a holding potential of −50 mV, under conditions in which the L‐type Ca2+ current (ICa,L) and IKr were inhibited; the effect was concentration‐dependent with an IC50 of 5.3 μM, when evaluated by the decrease in the amplitude of IKs tail current following 4‐s depolarizing voltage steps to +50 mV.
The 293B block of IKs progressed with time during depolarizing voltage steps with a more rapid block at higher concentrations.
The block of IKs by 293B was fully reversed within a few minutes after washing off the drug, even when a maximal effect (a nearly full block) was achieved at high drug concentration (50 μM).
Bath application of 293B at 50 μM greatly and reversibly reduced the amplitude of IKs which is maximally stimulated by β‐adrenergic agonist isoprenaline (1 μM), while the degree of 293B block of the isoprenaline‐stimulated IKs was slightly but significantly smaller than that of non‐stimulated IKs (94.0±0.98% block, n=6 vs 99.4±0.45% block, n=6; P<0.01).
We conclude that, in guinea‐pig SA node cells (i) 293B is a potent and fully reversible blocker of IKs in control and during β‐adrenergic stimulation and (ii) block with 293B occurs in a time‐dependent manner during depolarizing voltage steps.
In guinea‐pig sino‐atrial (SA) node cells the delayed rectifier K+ current (IK) is composed of rapidly and slowly activating components of IK (IKr and IKs, respectively). The present study was undertaken to characterize the blocking action of the chromanol derivative 293B on IKs in guinea‐pig SA node cells using whole‐cell patch‐clamp technique.
Bath application of 293B blocked IKs, elicited by 4‐s depolarizing voltage pulses from a holding potential of −50 mV, under conditions in which the L‐type Ca2+ current (ICa,L) and IKr were inhibited; the effect was concentration‐dependent with an IC50 of 5.3 μM, when evaluated by the decrease in the amplitude of IKs tail current following 4‐s depolarizing voltage steps to +50 mV.
The 293B block of IKs progressed with time during depolarizing voltage steps with a more rapid block at higher concentrations.
The block of IKs by 293B was fully reversed within a few minutes after washing off the drug, even when a maximal effect (a nearly full block) was achieved at high drug concentration (50 μM).
Bath application of 293B at 50 μM greatly and reversibly reduced the amplitude of IKs which is maximally stimulated by β‐adrenergic agonist isoprenaline (1 μM), while the degree of 293B block of the isoprenaline‐stimulated IKs was slightly but significantly smaller than that of non‐stimulated IKs (94.0±0.98% block, n=6 vs 99.4±0.45% block, n=6; P<0.01).
We conclude that, in guinea‐pig SA node cells (i) 293B is a potent and fully reversible blocker of IKs in control and during β‐adrenergic stimulation and (ii) block with 293B occurs in a time‐dependent manner during depolarizing voltage steps.
British Journal of Pharmacology (2002) 137, 253–262. doi:10.1038/sj.bjp.0704861
DOI: 10.1038/sj.bjp.0704861
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