Dihydropyridine Action on Voltage-dependent Potassium Channels Expressed in <i>Xenopus</i> Oocytes

Avdonin, Vladimir; Shibata, Erwin F.; Hoshi, Toshinori

doi:10.1085/jgp.109.2.169

Cited by 27 publications

(25 citation statements)

References 29 publications

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“…This phenomena has been reported for both native (Missan et al, 2003) and heterologously expressed (Zhang X 1997, Avdonin V and Hoshi T J Gen Physilo 1997) cardiac Kv channels. The pattern of voltage-dependent block described in cardiac Kv channels is consistent with an open channel block, whereby the blocker is “knocked-off” its binding site in the channel pore by K + leaving the cell under an ever increasing driving force.…”

Section: Discussionsupporting

confidence: 67%

“…Dihydropyridine-induced block of several Kv channels studied in heterologous expression systems, including Kv4.3 (Bett et al, 2006), Shaker (Kv1) family subunits (Avdonin et al, 1997) such as hKv1.5 channel (Zhang et al, 1997), involves open-channel block. Such a blocking mechanism is readily manifest as an increase in both the extent and rate of current decay during prolonged channel activation.…”

Section: Discussionmentioning

confidence: 99%

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Dihydropyridine block of voltage-dependent K+ currents in rat dorsal root ganglion neurons

Zhang

Gold

2009

Neuroscience

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The dihydropyridines nifedipine, nimodipine and Bay K 8644 are widely used as pharmacological tools to assess the contribution of L-type voltage-gated Ca 2+ channels to a variety of neuronal processes including synaptic transmission, excitability and second messenger signaling. These compounds are still used in neuronal preparations despite evidence from cardiac tissue and heterologous expression systems that they block several voltage-gated K + (Kv) channels. Both because these compounds have been used to assess the relative contribution of L-type Ca 2+ channels to several different processes in dorsal root ganglion (DRG) neurons and because a relatively wide variety of Kv channels present in other neuronal populations are present in DRG neurons, we determined the extent to which dihydropyridines block Kv currents in these neurons. Standard whole cell patch clamp techniques were used to study acutely disassociated adult rat DRG neurons. All three dihydropyridines tested blocked Kv currents in DRG neurons; IC 50 values for nifedipine and nimodipine-induce block of sustained Kv currents were 14.5 μM and 6.6 μM, respectively. The magnitude of sustained current block was 44 ± 1.6%, 60 ± 2%, and 56 ± 2.9% with 10 μM nifedipine, nimodipine and Bay K 8644, respectively. Current block was occluded by neither 4-aminopyridine (5 mM) nor tetraethylamonium (135 mM). Dihydropyridine-induced block of Kv currents was not associated with a shift in the voltage-dependence of current activation or inactivation, the recovery from inactivation, or voltage dependent block. However, there was a small use-dependence to the dihydropyridine-induced block. Our results suggest that several types of Kv channels in DRG neurons are blocked by mechanisms distinct from those underlying block of Kv channels in cardiac myocytes. Importantly, our results suggest that if investigators wish to explore the contribution of L-type Ca 2+ channels to neuronal function, they should consider alternative strategies for the manipulation of these channels than the use of dihydropyridines.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Dihydropyridine block of voltage-dependent K+ currents in rat dorsal root ganglion neurons

Zhang

Gold

2009

Neuroscience

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“…Whole-oocyte and macropatch recordings were performed essentially as described by Avdonin et al (23). The analysis of the deactivation kinetics and determination of the conductance-voltage (G-V) curves were performed without leak subtraction.…”

Section: Methodsmentioning

confidence: 99%

Voltage-dependent gating characteristics of the K ⁺ channel KAT1 depend on the N and C termini

Marten

Hoshi

1997

Proc. Natl. Acad. Sci. U.S.A.

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We studied how the C and N termini of the plant K ؉ channel KAT1 inf luence the voltage-dependent gating behavior by generating C-and N-terminal deletion mutants. Functional expression was observed only when Cterminal deletions were downstream of the putative cyclic nucleotide binding site. Treatments of oocytes expressing KAT1 channels with anticytoskeletal agents indicated that intact microtubules are important for functional expression. C-terminal deletions altered the voltage sensitivity of the KAT1 channel with greater deletions resulting in smaller equivalent charge movements. In contrast, a deletion in the N terminus (⌬20-34) shifted the half-activation voltage by approximately ؊65 mV without markedly affecting the number of equivalent charges. The results reveal novel roles of the N and C termini in regulation of the voltage-dependent gating of KAT1.The cloned plant potassium channels, KAT1, AKT1͞3, and KST1, functionally expressed in heterologous expression systems conduct inward currents upon hyperpolarization (1-7). Their amino acid sequences, however, are similar to those of the members of the Shaker superfamily such as the Drosophila eag channel, the human-related eag channel HERG and the cyclic nucleotide-gated (CNG) channel (5,6,8,9; for review, see ref. 10). The structural organization of the KAT1 channel consists of six putative membrane-spanning domains (S1-S6) with a putative voltage-sensing S4 segment and a P-region between S5 and S6. The N and C termini are likely to face the cytoplasm and thus are accessible by intracellular regulatory factors (4).Recent studies have shown that the members of the Shaker superfamily contain several definable functional domains. For example, the S4 and the S4-S5 linker segments appear to have major roles in voltage-sensing and activation (for review, see ref. 11). Some mutations in the S4 segment alter the equivalent charge movements associated with voltage-dependent activation (12). In contrast, the N-terminal domain is known to be important in N-type inactivation (13-15) and subunit assembly (16) while the C-terminal domain often contains regulatoryfactor binding domains as in Ca 2ϩ -dependent K ϩ channels (Slo) (17) and CNG channels (18). The KAT1 channel subunit has a short N terminus with one potential phosphorylation site and a long C terminus with several putative regulatory sites (Fig. 1). The sequence similarity between a region of the KAT1 C terminus and the cAMP-binding domain of the Escherichia coli catabolite gene activator protein (20) suggests the presence of a cyclic nucleotide binding site in KAT1. Further, the KAT1 C terminus is rich in potential phosphorylation sites mediated by cAMP͞cGMP-dependent protein kinases, Ca 2ϩ calmodulin-dependent kinase II or protein kinase C (19), and putative protonation sites (e.g., histidines). The KAT1 homologs AKT1, AKT2, and AKT3 contain an ankyrin repeat domain in the C-terminal region, indicating a potential cytoskeletal binding segment (6, 9, 21). BLAST sequence comparison of the KAT1 C-termina...

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“…117,118 By contrast, the nondihydropyridine CCB verapamil shortened the duration of the QT interval, whereas diltiazem did not change the duration of the QT interval in the setting of angina pectoris, 104 and appeared to prolong the interval in a small sample of hypertensive patients 119 (Table 3). Verapamil significantly shortened the QT interval at low heart rates in patients with structural normal hearts within 2 months after oral verapamil was prescribed for paroxysmal atrioventricular nodal reentrant tachycardia.…”

Section: Modulation Of Qt Interval Duration In Hypertension J Klimas mentioning

confidence: 96%

Modulation of the QT interval duration in hypertension with antihypertensive treatment

2015

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The duration of the QT interval as measured by 12-lead electrocardiography is a measure of myocardial repolarization and is widely used to describe cardiac abnormalities, to determine the presence of cardiac toxicity and to evaluate drug safety. In hypertension, the QT interval is a predictor of the risk of both coronary events and cardiovascular death, after adjusting for the effects of additional risk factors. The mechanism of QT interval prolongation is multifactorial and includes cardiomyocyte hypertrophy and increased left ventricular mass, with accompanying changes in left ventricular transmural dispersion of repolarization, as well as changes in the tone of the autonomic nervous system of some patients with hypertension and mechano-electrical feedback, although this mechanism is less likely. Antihypertensive drugs vary in their effect on QT interval duration. The mechanisms underlying their effect depend on changes in left ventricular mass and autonomic nervous system tone, as well as changes in the activity of cardiac ion channels. Although blood pressure reduction is the primary goal of antihypertensive drug therapy and although the choice of antihypertensive drug treatment regimens varies among different individuals, the data regarding the disparate effects of antihypertensive drugs on the duration of the QT interval warrant consideration when implementing long-term pharmacotherapy for hypertension.

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Dihydropyridine Action on Voltage-dependent Potassium Channels Expressed in Xenopus Oocytes

Cited by 27 publications

References 29 publications

Dihydropyridine block of voltage-dependent K+ currents in rat dorsal root ganglion neurons

Dihydropyridine block of voltage-dependent K+ currents in rat dorsal root ganglion neurons

Voltage-dependent gating characteristics of the K ⁺ channel KAT1 depend on the N and C termini

Modulation of the QT interval duration in hypertension with antihypertensive treatment

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Dihydropyridine Action on Voltage-dependent Potassium Channels Expressed in Xenopus Oocytes

Cited by 27 publications

References 29 publications

Dihydropyridine block of voltage-dependent K+ currents in rat dorsal root ganglion neurons

Dihydropyridine block of voltage-dependent K+ currents in rat dorsal root ganglion neurons

Voltage-dependent gating characteristics of the K + channel KAT1 depend on the N and C termini

Modulation of the QT interval duration in hypertension with antihypertensive treatment

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Product

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Voltage-dependent gating characteristics of the K ⁺ channel KAT1 depend on the N and C termini