Pacemaker Channels Produce an Instantaneous Current

Proenza, Catherine; Angoli, Damiano; Agranovich, Eugene; Macri, Vincenzo; Accili, Eric A.

doi:10.1074/jbc.m106974200

Cited by 101 publications

(130 citation statements)

References 43 publications

Supporting

Mentioning

114

Contrasting

Order By: Relevance

“…Accili and his colleagues have suggested that the expression of HCN2 channels is associated with the expression of an "instantaneous current" that is voltage insensitive over the tested voltage range and the magnitude of which is directly proportional to the amount of heterologously expressed HCN protein and that increased on coexpression with the regulatory subunit minK-related peptide 1 (Macri and Accili 2004;Proenza et al 2002). These authors concluded that HCN channels mediate a voltage-insensitive, instantaneous current through leaky channels.…”

Section: Assessment Of Three Methods For Isolating I Hmentioning

confidence: 99%

“…It has recently been demonstrated that in an expression system, the expression of g h is associated with a voltageinsensitive conductance, an instantaneous current (Macri and Accili 2004;Proenza et al 2002). If the expression of a voltage-sensitive g h is associated with a voltage-insensitive conductance in T and D stellate cells, then the magnitude of the voltage-insensitive, ZD7288-sensitive conductance would be expected to be related to the voltage-sensitive conductance.…”

Section: Voltage-insensitive Zd7288-sensitive Conductancementioning

confidence: 99%

See 1 more Smart Citation

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: 99%

Section: Voltage-insensitive Zd7288-sensitive Conductancementioning

confidence: 99%

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

“…9). This is not altogether surprising when one considers that HCN2 channels are partially open at this potential (Chen et al, 2001a) and may generate a voltage-independent current (Proenza et al, 2002;Macri and Accili, 2004;Proenza and Yellen, 2006). Another possible explanation for this effect is poor dendritic voltage control when recording from the soma, which could result from the nonisopotentiality of RTN neurons (Destexhe et al, 1996).…”

Section: Hcn2 Channels and Glur4-containing Ampa Receptors Are Presenmentioning

confidence: 98%

Dendritic HCN2 Channels Constrain Glutamate-Driven Excitability in Reticular Thalamic Neurons

Ying¹,

Fan²,

Abbas³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

“…3A). The difference in sensitivities has been attributed to at least two open states for HCN2 channels, one a "leaky" open state permeable to Cs + and the other a "normal" hyperpolarization-activated state sensitive to Cs + (Proenza et al 2002).…”

Section: Figmentioning

confidence: 99%

Hyperpolarization-Activated Current (I h) in Vestibular Calyx Terminals: Characterization and Role in Shaping Postsynaptic Events

Meredith

Benke

Rennie

2012

JARO

View full text Add to dashboard Cite

Calyx afferent terminals engulf the basolateral region of type I vestibular hair cells, and synaptic transmission across the vestibular type I hair cell/calyx is not well understood. Calyces express several ionic conductances, which may shape postsynaptic potentials. These include previously described tetrodotoxin-sensitive inward Na + currents, voltage-dependent outward K + currents and a K(Ca) current. Here, we characterize an inwardly rectifying conductance in gerbil semicircular canal calyx terminals (postnatal days 3-45), sensitive to voltage and to cyclic nucleotides. Using whole-cell patch clamp, we recorded from isolated calyx terminals still attached to their type I hair cells. A slowly activating, noninactivating current (I h ) was seen with hyperpolarizing voltage steps negative to the resting potential. External Cs + (1-5 mM) and ZD7288 (100 μM) blocked the inward current by 97 and 83 %, respectively, confirming that I h was carried by hyperpolarization-activated, cyclic nucleotide gated channels. Mean half-activation voltage of I h was −123 mV, which shifted to −114 mV in the presence of cAMP. Activation of I h was well described with a third order exponential fit to the current (mean time constant of activation, τ, was 190 ms at −139 mV). Activation speeded up significantly (τ0136 and 127 ms, respectively) when intracellular cAMP and cGMP were present, suggesting that in vivo I h could be subject to efferent modulation via cyclic nucleotide-dependent mechanisms. In current clamp, hyperpolarizing current steps produced a time-dependent depolarizing sag followed by either a rebound afterdepolarization or an action potential. Spontaneous excitatory postsynaptic potentials (EPSPs) became larger and wider when I h was blocked with ZD7288. In a three-dimensional mathematical model of the calyx terminal based on HodgkinHuxley type ionic conductances, removal of I h similarly increased the EPSP, whereas cAMP slightly decreased simulated EPSP size and width.

show abstract

Pacemaker Channels Produce an Instantaneous Current

Cited by 101 publications

References 43 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

Dendritic HCN2 Channels Constrain Glutamate-Driven Excitability in Reticular Thalamic Neurons

Hyperpolarization-Activated Current (I h) in Vestibular Calyx Terminals: Characterization and Role in Shaping Postsynaptic Events

Contact Info

Product

Resources

About