Voltage-gated sodium channels(VGSCs) are transmembrane proteins responsible for generation and conduction of action potentials in excitable cells.Physiological and pharmacological studies have demonstrated that VGSCs ...Voltage-gated sodium channels(VGSCs) are transmembrane proteins responsible for generation and conduction of action potentials in excitable cells.Physiological and pharmacological studies have demonstrated that VGSCs play a critical role in chronic pain associated with tissue or nerve injury.Many long-chain peptide toxins(60-76 amino acid residues) purified from the venom of Asian scorpion Buthus martensii Karsch(BmK) are investigated to be sodium channel-specific modulators.The α-like neurotoxins that can bind to receptor site 3 of sodium channels,named as BmK I and BmK abT,could induce nociceptive effects in rats.On the contrast,the β-like neurotoxins that can bind to receptor site 4 of sodium channels,named as BmK AS,BmK AS-1 and BmK IT2,could produce potent anti-nociceptive effects in animal pain models.BmK I could strongly prolong the fast inactivation of tetrodotoxin(TTX)-sensitive Na+ currents on the rat dorsal root ganglia(DRG) neurons together with the augmentation of peak current amplitude.However,BmK IT2 and BmK ASs,potently suppressed both the peak TTX-resistant and TTX-sensitive Na+ currents on rat small DRG neurons.Moreover,BmK ASs could decrease the excitability of small DRG neurons.Thus,the nociception/anti-nociception induced by scorpion neurotoxins may attribute to their distinct modulation on sodium channels in primary afferent sensory neurons.Therefore,the sodium channel-specific modulators from BmK venom could be used as not only pharmacological tools for better understanding the roles of VGSCs in pain signal conduction,but also lead molecules in the development of ideal analgesics targeting VGSCs.展开更多
Hyperpolarization-activated and cyclic nucleotide-gated(HCN) channels,distributing in a variety of tissues,especially in excitable cells such as heart cells and many kinds of neurons,have an important role in the modu...Hyperpolarization-activated and cyclic nucleotide-gated(HCN) channels,distributing in a variety of tissues,especially in excitable cells such as heart cells and many kinds of neurons,have an important role in the modulation of heart rate and neuronal excitability.Different from typical voltage-gated sodium channels and potassium channels,HCN channels were evoked inward currents when the cell was hyperpolarized.More and more recent studies have disclosed that HCN channels play important roles in the nervous system,which were linked with its special electrophysiological features as well as its regulatory effect on the cellular membrane excitability.HCN channels could be modulated by many factors including both extracellular molecules and intracellular signaling cascades,which made its functions complicated in the different condition.Based on its role,HCN channels are presumed to be a promising target for chronic pain and brain disorders.In this paper,we will focus on the advancement of roles of HCN channels in the neural system as well as its complex modulator factors.展开更多
基金grants from National Basic Research Development Program of China(No.2006CB500801)National Natural Sciences Foundation of China(No.30370446)
文摘Voltage-gated sodium channels(VGSCs) are transmembrane proteins responsible for generation and conduction of action potentials in excitable cells.Physiological and pharmacological studies have demonstrated that VGSCs play a critical role in chronic pain associated with tissue or nerve injury.Many long-chain peptide toxins(60-76 amino acid residues) purified from the venom of Asian scorpion Buthus martensii Karsch(BmK) are investigated to be sodium channel-specific modulators.The α-like neurotoxins that can bind to receptor site 3 of sodium channels,named as BmK I and BmK abT,could induce nociceptive effects in rats.On the contrast,the β-like neurotoxins that can bind to receptor site 4 of sodium channels,named as BmK AS,BmK AS-1 and BmK IT2,could produce potent anti-nociceptive effects in animal pain models.BmK I could strongly prolong the fast inactivation of tetrodotoxin(TTX)-sensitive Na+ currents on the rat dorsal root ganglia(DRG) neurons together with the augmentation of peak current amplitude.However,BmK IT2 and BmK ASs,potently suppressed both the peak TTX-resistant and TTX-sensitive Na+ currents on rat small DRG neurons.Moreover,BmK ASs could decrease the excitability of small DRG neurons.Thus,the nociception/anti-nociception induced by scorpion neurotoxins may attribute to their distinct modulation on sodium channels in primary afferent sensory neurons.Therefore,the sodium channel-specific modulators from BmK venom could be used as not only pharmacological tools for better understanding the roles of VGSCs in pain signal conduction,but also lead molecules in the development of ideal analgesics targeting VGSCs.
基金supported by the Beijing Municipal Natural Science Foundation(7142123)
文摘Hyperpolarization-activated and cyclic nucleotide-gated(HCN) channels,distributing in a variety of tissues,especially in excitable cells such as heart cells and many kinds of neurons,have an important role in the modulation of heart rate and neuronal excitability.Different from typical voltage-gated sodium channels and potassium channels,HCN channels were evoked inward currents when the cell was hyperpolarized.More and more recent studies have disclosed that HCN channels play important roles in the nervous system,which were linked with its special electrophysiological features as well as its regulatory effect on the cellular membrane excitability.HCN channels could be modulated by many factors including both extracellular molecules and intracellular signaling cascades,which made its functions complicated in the different condition.Based on its role,HCN channels are presumed to be a promising target for chronic pain and brain disorders.In this paper,we will focus on the advancement of roles of HCN channels in the neural system as well as its complex modulator factors.
