Modulation of Voltage-Gated Ca²⁺Current in Vestibular Hair Cells by Nitric Oxide

Abstract

Almanza A, Navarrete F, Vega R, Soto E. Modulation of voltagegated Ca 2ϩ current in vestibular hair cells by nitric oxide. J Neurophysiol 97: 1188Neurophysiol 97: -1195Neurophysiol 97: , 2007. First published December 20, 2006; doi:10.1152/jn.00849.2006. The structural elements of the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) signaling pathway have been described in the vestibular peripheral system. However, the functions of NO in the vestibular endorgans are still not clear. We evaluated the action of NO on the Ca 2ϩ currents in hair cells isolated from the semicircular canal crista ampullaris of the rat (P14 -P18) by using the whole cell and perforated-cell patch-clamp technique. The NO donors 3-morpholinosydnonimine (SIN-1), sodium nitroprusside (SNP), and ( In the presence of Nethylmaleimide (NEM), a sulfhydryl alkylating agent that prevents the S-nitrosylation reaction, the SNP effect on the Ca 2ϩ current was significantly diminished. These results demonstrated that NO inhibits in a voltage-independent manner the voltage-activated Ca 2ϩ current in rat vestibular hair cells by the activation of a cGMP-signaling pathway and through a direct action on the channel protein by a Snitrosylation reaction. The inhibition of the Ca 2ϩ current by NO may contribute to the regulation of the intracellular Ca 2ϩ concentration and hair-cell synaptic transmission.

Contraction by Ca2+ Influx via the L-Type Ca2+ Channel Voltage Window in Mouse Aortic Segments is Modulated by Nitric Oxide

“…Because NO also shifted the voltage-dependence of the window contraction in the presence of levcromakalim, it was hypothesized that NO, but not levcromakalim exerted a direct effect on the gating properties of the L-type Ca 2+ channel. Although it has been described that NO affects L-type Ca 2+ channels directly via S-nitrosylation (Almanza et al, 2007), an effect on the voltagedependent contraction has not been directly demonstrated yet. Hence, it is hypothesized that in mouse aortic segments NO changed the voltage-dependence of the contraction mediated by L-type Ca 2+ influx, probably via S-nitrosylation of the cysteine residues located in the gating part of the channel´s α1C-subunit.…”

“…Effects of NO and cGMP on L-type Ca 2+ current have been described before. They might occur via an indirect mechanism through a NO-cGMP-PKG pathway and/or a direct mechanism mediated by Snitrosylation (Almanza et al, 2007). The α1C-subunit of the L-type Ca 2+ channel contains more than 10 cysteine residues that modulate channel gating and is constitutively Snitrosylated in the mouse heart (Sun et al, 2006;Tamargo et al, 2010).…”

Lack of Tff3 Peptide Results in Hearing Impairment and Accelerated Presbyacusis

“…Several studies suggest that nitric oxide (NO) plays an essential role in the pathophysiology of the inner ear including inflammation and immune response [48]. NO also regulate intracellular Ca 2+ -concentration in the inner and outer hair cells, thus influencing their mechanical properties as well as neurotransmission at synapses of the auditory nerve [49]. TFF's intricate regulatory pathways via cytokines and transcription factors and their participation in anti-apoptosis and innate immune response [50] and recently reviewed possible manifestation of UC in the nervous system [18] may serve as a lead for understanding their function in the inner ear.…”

Mechanisms of xylanase-induced nitric oxide and phosphatidic acid production in tomato cells

“…In plants, S-nitrosylation of proteins has attracted much less attention. However, there is substantial evidence regarding the in vivo effect of treatment with NEM in both the animal (Almanza et al 2007;Jian et al 2007;Pan et al 2008;Tjong et al 2008;Fig. 3 Staurosporine prevents xylanase stimulation of NO formation.…”

“…We found that exposure to up to 100 lM NEM had no effect on NO-mediated PA accumulation (data not shown). This unexpected result can be explained by analyzing the data in animals, where the applied doses of NEM ranged from 2 to 50 times higher the concentration of the NO donor applied (Almanza et al 2007;Jian et al 2007;Pan et al 2008;Tjong et al 2008;Kawano et al 2009). Taking data into consideration, the application of at least 1 mM NEM could probably attenuate the positive effect of 0.5 mM S-nitroso-N-acetylpenicillamine on PA accumulation in tomato cell suspensions.…”