Action of the hyperpolarization-activated current ( I h ) blocker ZD 7288 in hippocampal CA1 neurons

Gasparini, Sonia; DiFrancesco, Dario

doi:10.1007/s004240050488

Cited by 211 publications

(171 citation statements)

References 30 publications

Supporting

Mentioning

146

Contrasting

Unclassified

Order By: Relevance

“…In contrast to the present results, the instantaneous current was insensitive to extracellular Cs ϩ , but its sensitivity to ZD7288 was not reported. In hippocampal pyramidal cells ZD7288, at 10 -20 M, blocked ϳ18% of the resting conductance (Gasparini and DiFrancesco 1997). Other authors, however, did not observe an instantaneous, ZD7288-sensitive conductance in thalamic relay neurons (Luthi et al 1998) and with coexpression of HCN with the MiRP1 protein in cardiac sinoatrial cells (Qu et al 2004).…”

Section: Assessment Of Three Methods For Isolating I Hmentioning

confidence: 89%

“…At 50 M, ZD7288 has been reported to block glutamate receptors of both AMPA and N-methyl-D-aspartate (NMDA) subtypes (Chen 2004) and a low-voltage-activated Ca 2ϩ conductance (Felix et al 2003), but these conductances were blocked by DNQX and by voltage, respectively, in our experiments. In hippocampal pyramidal cells and in thalamic relay neurons, neither Na ϩ -nor Ca 2ϩ -dependent action potentials were affected by ZD7288 (Gasparini and DiFrancesco 1997;Luthi et al 1998;Maccaferri and McBain 1996). Furthermore, the removal of Ca 2ϩ does not affect the resting potential or the shape of action potentials in T stellate cells (Wickesberg and Oertel 1989), indicating that voltage-sensitive Ca 2ϩ conductances are small.…”

Section: Assessment Of Three Methods For Isolating I Hmentioning

confidence: 94%

“…This drug has been used to assay I h in octopus cells of the VCN (Bal and Oertel 2000), substantia nigra neurons (Harris and Constanti 1995), CA1 hippocampal pyramidal cells (Gasparini and DiFrancesco 1997;Macaferri and McBain 1996), thalamic neurons (Luthi et al 1998), and cerebellar basket cells (Saitow and Konishi 2000). In hippocampal CA1 neurons, the half-maximal blocking of I h required 10.5 M, and at 50 M, the concentration used in the present experiments, the block was nearly saturated (Gasparini and DiFrancesco 1997). At 50 M, ZD7288 has been reported to block glutamate receptors of both AMPA and N-methyl-D-aspartate (NMDA) subtypes (Chen 2004) and a low-voltage-activated Ca 2ϩ conductance (Felix et al 2003), but these conductances were blocked by DNQX and by voltage, respectively, in our experiments.…”

Section: Assessment Of Three Methods For Isolating I Hmentioning

confidence: 99%

“…In other cells, ZD7288 (BoSmith et al 1993;Gasparini and DiFrancesco 1997;Harris and Constanti 1995) and Cs ϩ (Harris and Constanti 1995;Magee 1998;McCormick and Pape 1990b) have been shown to block I h . We examined the sensitivity of the currents activated from a holding potential of Ϫ62 mV to 50 M ZD7288.…”

Section: Pharmacological Block By Zd7288 and Cs ϩmentioning

confidence: 99%

See 3 more Smart Citations

Hyperpolarization-Activated Currents Regulate Excitability in Stellate Cells of the Mammalian Ventral Cochlear Nucleus

Rodrigues¹,

Oertel²

2006

Journal of Neurophysiology

View full text Add to dashboard Cite

Rodrigues, Aldo Rogelis A. and Donata Oertel. Hyperpolarizationactivated currents regulate excitability in stellate cells of the mammalian ventral cochlear nucleus. J Neurophysiol 95: 76 -87, 2006. First published September 28, 2005 doi:10.1152/jn.00624.2005. The differing biophysical properties of neurons the axons of which form the different pathways from the ventral cochlear nucleus (VCN) determine what acoustic information they can convey. T stellate cells, excitatory neurons the axons of which project locally and to the inferior colliculus, and D stellate cells, inhibitory neurons the axons of which project to the ipsi-and contralateral cochlear nuclei, fire tonically when they are depolarized, and, unlike other cell types in the VCN, their firing rates are sensitive to small changes in resting currents. In both types of neurons, the hyperpolarization-activated current (I h ) reversed at -40 mV, was activated at voltages negative to Ϫ60 mV, and half-activated at approximately Ϫ88 mV; maximum hyperpolarization-activated conductances (g h max ) were 19.1 Ϯ 2.3 nS in T and 30.3 Ϯ 2.6 nS in D stellate cells (means Ϯ SE). Activation and deactivation were slower in T than in D stellate cells. In both types of stellate cells, 50 M 4(N-ethyl-N-phenylamino)1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288) and 2 mM Cs ϩ blocked a 6-to 10-fold greater conductance than the voltage-dependent g h determined from Boltzmann analyses at -62 mV. The voltageinsensitive, ZD7288-sensitive conductance was proportional to g h max and g input . 8-Br-cAMP shifted the voltage dependence of I h in the depolarizing direction, increased the rate of activation, and slowed its deactivation in both T and D stellate cells. Reduction in temperature did not change the voltage dependence but reduced the maximal g h with a Q 10 of 1.3 and slowed the kinetics with a Q 10 of 3.3.

show abstract

Section: Assessment Of Three Methods For Isolating I Hmentioning

confidence: 89%

Section: Assessment Of Three Methods For Isolating I Hmentioning

confidence: 94%

Section: Assessment Of Three Methods For Isolating I Hmentioning

confidence: 99%

Section: Pharmacological Block By Zd7288 and Cs ϩmentioning

confidence: 99%

See 2 more Smart Citations

Hyperpolarization-Activated Currents Regulate Excitability in Stellate Cells of the Mammalian Ventral Cochlear Nucleus

Rodrigues¹,

Oertel²

2006

Journal of Neurophysiology

View full text Add to dashboard Cite

show abstract

“…Several f-channel blocker molecules have been developed, such as UL-FS49 (Goethals et al, 1993;DiFrancesco, 1994), ZD7288 (BoSmith et al, 1993;Gasparini and DiFrancesco, 1997;Shin et al, 2001), and ivabradine (Thollon et al, 1994;Bois et al, 1996). These molecules have been shown to induce heart rate slowing with limited inotropic side effects, and have therefore a potential for therapeutic application in those cases where it is useful to slow heart rate without altering other cardiovascular functions.…”

Section: Introductionmentioning

confidence: 99%

Abstracts of Papers at the Fifty-Sixth Annual Meeting of the Society of General Physiologists

2002

The Journal of General Physiology

View full text Add to dashboard Cite

"Funny" (f-) channels have a key role in generation of spontaneous activity of pacemaker cells and mediate autonomic control of cardiac rate; f-channels and the related neuronal h-channels are composed of hyperpolarization-activated, cyclic nucleotide-gated (HCN) channel subunits. We have investigated the block of f-channels of rabbit cardiac sino-atrial node cells by ivabradine, a novel heart rate-reducing agent. Ivabradine is an open-channel blocker; however, block is exerted preferentially when channels deactivate on depolarization, and is relieved by long hyperpolarizing steps. These features give rise to use-dependent behavior. In this, the action of ivabradine on f-channels is similar to that reported of other rate-reducing agents such as UL-FS49 and ZD7288. However, other features of ivabradine-induced block are peculiar and do not comply with the hypothesis that the voltage-dependence of block is entirely attributable to either the sensitivity of ivabradine-charged molecules to the electrical field in the channel pore, or to differential affinity to different channel states, as has been proposed for UL-FS49 (DiFrancesco, D. 1994. Pflugers Arch. 427:64-70) and ZD7288 (Shin, S.K., B.S. Rotheberg, and G. Yellen. 2001. J. Gen. Physiol. 117:91-101), respectively. Experiments where current flows through channels is modified without changing membrane voltage reveal that the ivabradine block depends on the current driving force, rather than voltage alone, a feature typical of block induced in inwardly rectifying K ϩ channels by intracellular cations. Bound drug molecules do not detach from the binding site in the absence of inward current through channels, even if channels are open and the drug is therefore not "trapped" by closed gates. Our data suggest that permeation through f-channel pores occurs according to a multiion, single-file mechanism, and that block/unblock by ivabradine is coupled to ionic flow. The use-dependence resulting from specific features of I f block by ivabradine amplifies its rate-reducing ability at high spontaneous rates and may be useful to clinical applications.

show abstract

The “Funny” Pacemaker Current

Barbuti¹,

Bucchi²,

Baruscotti³

et al. 2009

Novel Therapeutic Targets for Antiarrhythmic Drugs

View full text Add to dashboard Cite

Action of the hyperpolarization-activated current ( I h ) blocker ZD 7288 in hippocampal CA1 neurons

Cited by 211 publications

References 30 publications

Hyperpolarization-Activated Currents Regulate Excitability in Stellate Cells of the Mammalian Ventral Cochlear Nucleus

Hyperpolarization-Activated Currents Regulate Excitability in Stellate Cells of the Mammalian Ventral Cochlear Nucleus

Abstracts of Papers at the Fifty-Sixth Annual Meeting of the Society of General Physiologists

The “Funny” Pacemaker Current

Contact Info

Product

Resources

About