Differences in outward currents between neonatal and adult rabbit ventricular cells

Sánchez-Chapula, José A.; Elizalde, Alejandro; Navarro‐Polanco, Ricardo A.; Barajas, Hector

doi:10.1152/ajpheart.1994.266.3.h1184

Cited by 23 publications

(21 citation statements)

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“…[25][26][27] Quinidine's effect on I K1 also has been reported to be age-dependent in rabbits, with the neonatal current being more sensitive to inhibition by the quinidine when compared with the adult current. 7 However, rabbit I K1 has been shown to undergo significant developmental changes, 28,29 whereas no such developmental changes have been demonstrated for human I K1 . 12 These results indicate that species-related differences in channel expression and the pattern of postnatal changes exist for both I to and I K1 in mammalian cardiac tissue.…”

Section: Comparison Of Results With Previous Studiesmentioning

confidence: 99%

Quinidine Interactions With Human Atrial Potassium Channels

Nenov

Crumb

Pigott

et al. 1998

Circulation Research

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Abstract-Clinical studies have suggested that quinidine is less effective when used for the treatment of atrial arrhythmias in pediatric patients compared with its clinical effectiveness in the adult patient population. Age-related changes in the cardiac actions of quinidine on action potential duration and interaction with potassium channels in several mammalian species also have been reported. We investigated the effects of postnatal development on quinidine's interaction with major repolarizing currents (I to , I Kur , I ns , and I K1 ) in human atrial myocytes, using the whole-cell configuration of the voltage-clamp technique. Our results indicate that there are age-related changes in both the IC 50 for quinidine blockade of I to , as well as the mechanism of quinidine unblocking. In contrast, quinidine was found to inhibit both adult and pediatric I K1 and I Kur in an age-independent manner, whereas the nonselective cation current (I ns ), which contributes to the sustained outward current (I sus ), was insensitive to quinidine. The results from this study help to clarify the electrophysiological mechanism by which quinidine elicits its antiarrhythmic effect in the pediatric and adult human population. (Circ Res. 1998;83:1224-1231.)uinidine is one of the most commonly used drugs for treatment of both atrial and ventricular rhythm disturbances. 1 Quinidine's efficacy as an antiarrhythmic agent is believed to result from its effects on conduction velocity and repolarization of the cardiac action potential. 1,2 Quinidine's ability to prolong the duration of the cardiac action potential has been attributed to its ability to inhibit several different types of potassium ion channels expressed in mammalian cardiac tissue, including the transient outward K current (I to ), the inwardly rectifying K current (I K1 ), the rapidly activating delayed rectifier (I Kr ), and the ultrarapid delayed rectifier (I Kur ). 3 However, the mechanisms by which quinidine exerts its inhibitory effects on these potassium currents are not understood fully.Previous studies in dog, rabbit, and rat cardiac tissue have documented that the ability of quinidine and other antiarrhythmic agents to alter conduction and repolarization change significantly during postnatal development. 4 -8 Quinidine has been shown to prolong both the QT interval 9 and repolarization 4 of the Purkinje fiber action potential to a significantly greater extent in young canines compared with adult animals. Recent evidence suggests that developmental changes in the effects of antiarrhythmic agents on cardiac tissue may be attributed to age-related changes in drug-channel interactions. 6 -8 For example, quinidine block of rabbit ventricular I to and I K1 has been shown to be significantly different in neonatal versus adult myocytes, with cells from neonates being more sensitive to the action of quinidine than adults. 8 It seems likely that age-related differences in quinidine interaction with cardiac ion channels may also exist in man. Recent clinical studies have d...

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Section: Comparison Of Results With Previous Studiesmentioning

confidence: 99%

Quinidine Interactions With Human Atrial Potassium Channels

Nenov

Crumb

Pigott

et al. 1998

Circulation Research

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“…Isolated atrial and ventricular myocytes Isolated left atrial myocytes from adult cats (> 3 kg) were prepared using an enzymatic perfusion method (SAnchez-Chapula, Elizalde, Navarro-Polanco & Barajas, 1994). The animals were anaesthetized with sodium pentobarbitone (35 mg kg-', i.P.)…”

Section: Methodsmentioning

confidence: 99%

4‐aminopyridine activates potassium currents by activation of a muscarinic receptor in feline atrial myocytes.

Navarro‐Polanco

Sánchez-Chapula

1997

The Journal of Physiology

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1. The effects of 4-aminopyridine (4-AP) on action potentials, macroscopic membrane currents and single-channel recording from cardiac left atrial myocytes of the adult cat were studied using the whole-cell and cell-attached configurations of the patch-clamp technique. 2. 4-AP (1 mM) produced a hyperpolarization of the resting membrane potential and a shortening of action potential duration. Under voltage-clamp conditions, we have found that 4-AP increased a background current and a delayed rectifier outward current. These effects were antagonized by atropine. In addition, both effects seemed to be mediated through a pertussis toxin-sensitive G protein.3. The background current induced by 4-AP displayed properties that are highly similar to those of the inwardly rectifying potassium current activated by acetylcholine ('K(ACh)). The time-dependent potassium current activated by 4-AP has kinetic and pharmacological properties different from those of the delayed rectifier potassium current previously identified in cardiac myocytes. 4. The activation of the delayed rectifier-like potassium current could be explained by the activation of a novel muscarinic receptor subtype in which acetylcholine acts as the antagonist. Another possibility is that 4-AP activates IK(ACh) in a time-and voltagedependent manner.

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“…In the neonatal myocardium, the AP is longer than in the adult, and AP shortening with maturation coincides with an increase in myocardial I to density and channel isoform switch (28). Rabbit ventricle also shows a developmental increase I to and calcium homeostasis in the heart in I to , but in this species the dominant component shifts from I to,f to I to,s (29). On the other hand, aging is associated with a decrease in I to density and AP prolongation (30).…”

Section: Developmental Stagementioning

confidence: 96%