Role of the Hyperpolarization‐Activated Cation Current (<i>I</i><sub>h</sub>) in Pacemaker Activity in Area Postrema Neurons of Rat Brain Slices

Funahashi, Makoto; Mitoh, Yoshihiro; Kohjitani, Atsushi; Matsuo, Ryuji

doi:10.1113/jphysiol.2003.047191

Cited by 56 publications

(50 citation statements)

References 55 publications

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“…AP neurons in this preparation exhibited membrane properties and patterns of activity similar to those of acutely dissociated neurons prepared by others (Hay et al, 1996) and neurons from acute slices (Jahn et al, 1996;Funahashi et al, 2003;present study). Although cells maintained for longer periods were not used in this study, the observation that these cultured AP neurons can be maintained for several weeks (our unpublished observations) attests to the suitability of these cells.…”

Section: Discussionmentioning

confidence: 71%

Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Fry¹,

Smith²,

Hoyda³

et al. 2006

J. Neurosci.

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Adiponectin is an adipocyte-derived peptide hormone involved in energy homeostasis and the pathogenesis of obesity, including hypertension. Area postrema (AP) lacks a blood-brain barrier and is a critical homeostatic integration center for humoral and neural signals. Here we investigate the role of AP in adiponectin signaling. We show that rat AP expresses AdipoR1 and AdipoR2 adiponectin receptor mRNA. We used current-clamp electrophysiology to investigate whether adiponectin influenced membrane properties of AP neurons and found that ϳ60% of rat AP neurons tested were sensitive to adiponectin. Additional electrophysiology experiments coupled with single-cell reverse transcription-PCR indicated that all neurons that expressed both subtypes of receptor were sensitive to adiponectin, whereas neurons expressing only one subtype were predominantly insensitive. Last, microinjection of adiponectin into AP caused significant increases in arterial blood pressure, with no change in heart rate, suggesting that adiponectin acts at AP to provide a possible link between control of energy homeostasis and cardiovascular function.

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Section: Discussionmentioning

confidence: 71%

Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Fry¹,

Smith²,

Hoyda³

et al. 2006

J. Neurosci.

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“…These blockers are commonly used to inhibit I h channel activity (Aponte et al 2006;Bayliss et al 1994;Funahashi et al 2003;Harris and Constanti 1995). To determine the role of calcium in the raised K ϩ -mediated depression of EP neuronal activity observed in washout, slices were perfused for 5 min with 0 Ca 2ϩ aCSF prior to and throughout bath perfusion of 6 mM K ϩ .…”

Section: Experimental Protocolmentioning

confidence: 99%

“…To measure whole cell I h currents, slices were bath perfused for 5 min in I h "isolation solution" used by Funahashi et al (2003) containing (in mM): 104 NaCl, 20 tetraethylammonium, 2.5 KCl, 1 BaCl 2 , 1 MgCl 2 , 26 NaHCO 3 , 2 4-aminopyridine, 0.001 TTX, 25 D-glucose, and 1 CoCl 2 , prior to and during voltage-clamp experiments. EP neurons were initially voltage-clamped to Ϫ60 mV and then stepped down to Ϫ140 mV for 1 s in 10-mV increments.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…EP neurons were initially voltage-clamped to Ϫ60 mV and then stepped down to Ϫ140 mV for 1 s in 10-mV increments. A 1-s step duration of the voltage-clamp was required to allow for stable current values since these channels have slow activating and deactivating kinetics (Aponte et al 2006;Funahashi et al 2003;Harris and Constanti 1995). The I h current was measured from the instantaneous current (current value 5-10 ms after the inward capacitative transient; Funahashi et al 2002) to the steady-state constant current (value at the end of the current trace prior to release of the voltage-clamp).…”

Section: Experimental Protocolmentioning

confidence: 99%

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Enhanced I_h Depresses Rat Entopeduncular Nucleus Neuronal Activity From High-Frequency Stimulation or Raised K_e⁺

Shin¹,

Carlen²

2008

Journal of Neurophysiology

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Shin DS, Carlen PL. Enhanced I h depresses rat entopeduncular nucleus neuronal activity from high-frequency stimulation or raised K e ϩ . J Neurophysiol 99: 2203-2219, 2008. First published February 27, 2008 doi:10.1152/jn.01065.2007. High-frequency stimulation (HFS) is used to treat a variety of neurological diseases, yet its underlying therapeutic action is not fully elucidated. Previously, we reported that HFS-induced elevation in [K ϩ ] e or bath perfusion of raised K e ϩ depressed rat entopeduncular nucleus (EP) neuronal activity via an enhancement of an ionic conductance leading to marked depolarization. Herein, we show that the hyperpolarization-activated (I h ) channel mediates the HFS-or K ϩ -induced depression of EP neuronal activity. The perfusion of an I h channel inhibitor, 50 M ZD7288 or 2 mM CsCl, increased input resistance by 23.5 Ϯ 7% (ZD7288) or 35 Ϯ 10% (CsCl), hyperpolarized cells by 3.4 Ϯ 1.7 mV (ZD7288) or 2.3 Ϯ 0.9 mV (CsCl), and decreased spontaneous action potential (AP) frequency by 51.5 Ϯ 12.5% (ZD7288) or 80 Ϯ 13.5% (CsCl). The I h sag was absent with either treatment, suggesting a block of I h channel activity. Inhibition of the I h channel prior to HFS or 6 mM K ϩ perfusion not only prevented the previously observed decrease in AP frequency, but increased neuronal activity. Under voltage-clamp conditions, I h currents were enhanced in the presence of 6 mM K ϩ . Calcium is also involved in the depression of EP neuronal activity, since its removal during raised K e ϩ application prevented this attenuation and blocked the I h sag. We conclude that the enhancement of I h channel activity initiates the HFS-and K ϩ -induced depression of EP neuronal activity. This mechanism could underlie the inhibitory effects of HFS used in deep brain stimulation in output basal ganglia nuclei.

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“…Bath application of Ba 2ϩ (200 M) was used to block I Kir(rest) and I Kir in the present study. It is noted that 1) although Ba 2ϩ is not specific for K ir currents, no other K ϩ currents are responsible for the inward rectification at the membrane jpet.aspetjournals.org potential levels more negative than the RMP, and 2) the hyperpolarization-activated cation current (I h ) is insensitive to Ba 2ϩ , although it may also contribute to the inward rectification (Funahashi et al, 2003). Although the RMP appeared to be unchanged following repeated cocaine administration (Table 1), application of Ba 2ϩ significantly depolarized the RMP in both saline-and cocaine-pretreated mPFC neurons (SAL/Control: Ϫ67.46 Ϯ 0.97 mV versus SAL/ Ba 2ϩ : Ϫ59.83 Ϯ 1.08 mV, n ϭ 6 cells; p Ͻ 0.01; paired t test and COC/Control: Ϫ68.39 Ϯ 0.82 mV versus COC/Ba 2ϩ : Ϫ64.64 Ϯ 0.73 mV, n ϭ 6 cells; p Ͻ 0.01; paired t test) (Fig.…”

Section: Repeated Administration Of Cocaine Decreased the Effects Of Bamentioning

confidence: 99%

Repeated Cocaine Administration Increases Membrane Excitability of Pyramidal Neurons in the Rat Medial Prefrontal Cortex

Nasif¹,

Sidiropoulou²,

Hu³

et al. 2004

J Pharmacol Exp Ther

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Although the medial prefrontal cortex (mPFC) plays a critical role in cocaine addiction, the effects of chronic cocaine on mPFC neurons remain poorly understood. Here, we performed visualized current-clamp recordings to determine the effects of repeated cocaine administration on the membrane excitability of mPFC pyramidal neurons in rat brain slices. Following repeated cocaine administration (15 mg/kg/day i.p. for 5 days) with a 3-day withdrawal, alterations in membrane properties, including increased input resistance, reduced intensity of intracellular injected currents required for generation of Na ϩ -dependent spikes (rheobase), and an increased number of spikes evoked by depolarizing current pulses were observed in mPFC neurons. The current-voltage relationship was also altered in cocaine-pretreated neurons showing reduced outward rectification during membrane depolarization and decreased inward rectification during membrane hyperpolarization. Application of the K ϩ channel blocker Ba 2ϩ depolarized the resting membrane potential (RMP) and enhanced membrane potential response to injection of hyperpolarizing current pulses. However, the effects of Ba 2ϩ on RMP and hyperpolarized membrane potentials were significantly attenuated in cocaine-withdrawn neurons compared with saline-pretreated cells. These findings indicate that repeated cocaine administration increased the excitability of mPFC neurons after a short-term withdrawal, possibly via reducing the activity of the potassium inward rectifiers (K ir ) and voltage-gated K ϩ currents. Similar changes were also observed in cocaine-pretreated mPFC neurons after a long-term (2-3 weeks) withdrawal, revealing a persistent increase in excitability. These alterations in mPFC neuronal excitability may contribute to the development of behavioral sensitization and withdrawal effects following chronic cocaine exposure.

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Role of the Hyperpolarization‐Activated Cation Current (I_h) in Pacemaker Activity in Area Postrema Neurons of Rat Brain Slices

Cited by 56 publications

References 55 publications

Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Enhanced I_h Depresses Rat Entopeduncular Nucleus Neuronal Activity From High-Frequency Stimulation or Raised K_e⁺

Repeated Cocaine Administration Increases Membrane Excitability of Pyramidal Neurons in the Rat Medial Prefrontal Cortex

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Role of the Hyperpolarization‐Activated Cation Current (Ih) in Pacemaker Activity in Area Postrema Neurons of Rat Brain Slices

Cited by 56 publications

References 55 publications

Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Area Postrema Neurons Are Modulated by the Adipocyte Hormone Adiponectin

Enhanced Ih Depresses Rat Entopeduncular Nucleus Neuronal Activity From High-Frequency Stimulation or Raised Ke+

Repeated Cocaine Administration Increases Membrane Excitability of Pyramidal Neurons in the Rat Medial Prefrontal Cortex

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Role of the Hyperpolarization‐Activated Cation Current (I_h) in Pacemaker Activity in Area Postrema Neurons of Rat Brain Slices

Enhanced I_h Depresses Rat Entopeduncular Nucleus Neuronal Activity From High-Frequency Stimulation or Raised K_e⁺