The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies

Transient receptor potential(TRP)channels are one primary type of calcium(Ca^(2+))permeable channels,and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems.Nowadays,however,accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression,inducing tumor invasion and metastasis.However,the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive.Therefore,in this review,we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance(MDR),metastasis,apoptosis,proliferation,immune surveillance evasion,and the alterations of relevant tumor micro-environment.Moreover,we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’efficacy.The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented.Furthermore,it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.

Local neuronal circuits that may shape the discharge patterns of inferior collicular neurons

The discharge patterns of neurons in auditory centers encode information about sounds.However,few studies have focused on the synaptic mechanisms underlying the shaping of discharge patterns using intracellular recording techniques.Here,we investigated the discharge patterns of inferior collicular（IC）neurons using intracellular recordings to further elucidate the mechanisms underlying the shaping of discharge patterns.Under in vivo intracellular recording conditions,recordings were obtained from 66 IC neurons in 18 healthy adult mice（Mus musculus,Km）under free field-stimulation.Fiftyeight of these neurons fired bursts of action potentials（APs）to auditory stimuli and the remaining eight just generated local responses such as excitatory（n=4）or inhibitory（n=4）postsynaptic potentials.Based on the APs and subthreshold responses,the discharge patterns were classified into seven types：phasic（24/58,41.4%）,phasic burst（8/58,13.8%）,pauser（4/58,6.9%）,phasic-pauser（1/58,1.7%）,chopper（2/58,3.4%）,primary-like tonic（14/58,24.1%）and sound-induced inhibitory（5/58,8.6%）.We concluded that（1）IC neurons exhibit at least seven distinct discharge patterns;（2）inhibition participates in shaping the discharge pattern of most IC neurons and plays a role in sculpting the pattern,except for the primary-like tonic pattern which was not shapedby inhibition;and（3）local neural circuits are the likely structural basis that shapes the discharge patterns of IC neurons and can be formed either in the IC or in lower-level auditory structures.