HCN channels contribute to the intrinsic activity of cochlear pyramidal cells

Abstract

A hyperpolarization-activated current recorded from the pyramidal cells of the dorsal cochlear nucleus was investigated in the present study by using 150- to 200-microm-thick brain slices prepared from 6- to 14-day-old Wistar rats. The pyramidal neurones exhibited a slowly activating inward current on hyperpolarization. The reversal potential of this component was -32 +/- 3 mV (mean +/- SE, n = 6), while its half-activation voltage was -99 +/- 1 mV with a slope factor of 10.9 +/- 0.4 mV (n = 27). This current was highly sensitive to the extracellular application of both 1 mM Cs+ and 10 microM ZD7288. The electrophysiological properties and the pharmacological sensitivity of this current indicated that it corresponded to a hyperpolarization-activated non-specific cationic current (Ih). Our experiments showed that there was a correlation between the availability of the h-current and the spontaneous activity of the pyramidal cells, suggesting that this conductance acts as a pacemaker current in these neurones. Immunocytochemical experiments were also conducted on freshly isolated pyramidal cells to demonstrate the possible subunit composition of the channels responsible for the genesis of the pyramidal h-current. These investigations indicated the presence of HCN1, HCN2 and HCN4 subunits in the pyramidal cells.

Serotonin modulates response properties of neurons in the dorsal cochlear nucleus of the mouse

“…A thorough characterization of 5-HT effects on DCN neurons in vitro revealed strong increases in neuronal excitability through 5-HT 2A/2C and 5-HT 7 receptors via augmentation of the I h current of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (Tang and Trussell, 2015). The majority of our recordings were consistent with this finding, as the application of 5-HT acted to significantly increase the rate of both spontaneous and evoked spiking in the same neurons, supporting a role for depolarizing current through HCN channels in these cases (Pal et al, 2003). Because the 5-HT 2A R has been implicated in increasing neuronal excitability in the DCN in vitro (Tang and Trussell, 2015) and the IC in vivo (Hurley, 2006), we compared the effects of 5-HT with those of the 5-HT 2A/2C R agonist DOI.…”

Alterations in the spontaneous discharge patterns of single units in the dorsal cochlear nucleus following intense sound exposure

“…While some have asserted that cartwheel cells may fire in bursts in vivo, bursting activity has also been observed occasionally in cells at depths outside the range in which cartwheel cells are normally distributed in the DCN (Parham and Kim, 1995). Bursting activity has also been observed occasionally on cells that have the physiological characteristics of fusiform cells (Ding et al, 1999; Pal et al, 2003; Rhode and Smith, 1986). In our sample, bursting activity was often observed in units displaying type III frequency response areas (Fig.…”

“…Increases in spike duration have been shown to result when potassium channels are blocked (Zhang, et al, 2004). Down-regulation of the A-type potassium (IA) conductance, a prominent conductance in fusiform cells (Manis, 1990; Serodio and Rudy, 1998; Kanold and Manis, 1999; Pal, et al, 2003) is associated with hypersensitivity in pain (Hu et al, 2006) and increased bursting in pyramidal neurons in the electrosensory lateral line lobe (Ellis, et al, 2007), which are likely homologous to DCN fusiform cells (Mugnaini and Maler, 1993). Persistent sodium channels (I NaP ) are exhibited by DCN fusiform cells (Manis et al, 2003) and cause subthreshold membrane potential oscillations that could increase generation of burst firing.…”

“…Persistent sodium channels (I NaP ) are exhibited by DCN fusiform cells (Manis et al, 2003) and cause subthreshold membrane potential oscillations that could increase generation of burst firing. Fusiform cells also exhibit hyperpolarization-activated mixed cationic conductances (I h ; Mouse: Pal et al, 2003; Guinea Pig: Manis, 1990). An up-regulation of either I h or I NaP would increase excitability and spontaneous activity.…”

Nicotine-Mediated ADP to Spike Transition: Double Spiking in Septal Neurons

“…The discovery of i K2 subsequently underwent extensive interpretations by these and other authors (Vassalle et al 1995). Recurrent activation of HCN channels (DiFrancesco et al 1991; Luthi and McCormick 1998) leads to rhythmic spiking in diverse cells (Mao et al 2003; Pal et al 2003), and during developmental stages of the brain it triggers GDP—giant depolarizing potentials (Bender et al 2005). Both the involvement of HCN to and its altered expression in seizures depend on specific brain areas and underlying subunits/isoforms (Adams et al 2009).…”