Anti-TRPC4 (aa 948-960) polyclonal antibody

TRPC4 proteins form receptor-operated cation channels that are activated in synergy by M-2 and M-3 ACh receptors coupled to G(q/11) and G(i/o) proteins, respectively. These channels are widely expressed in the brain and smooth muscles where they perform a number of important functions, including control of GABA release from the dendrites and cholinergic excitation of smooth muscles. The biophysical properties of TRPC4 currents directly activated by GTP gamma S in mouse cells remain mostly unknown. We, thus, aimed to investigate these channels in mouse ileal myocytes where a prominent TRPC4-mediated cation current termed mI(CAT) is observed, and to compare the behavior of this current to that of the better studied mI(CAT) in guinea-pig myocytes. Although cation current responses to carbachol at -50 mV (i.e., at the value close to the normal resting potential in these cells) were highly similar, mI(CAT) in the mouse lacked the permissive action of intracellular Ca2+ on channel opening. The slope factor of the muscarinic cation conductance, which is a defining property of voltage-dependent behavior, was identical in both species. There were differences in the potential at which the current peaked at negative potentials, but not in the maximal current densities. Major differences were found in the kinetics of mI(CAT) voltagedependent relaxations, which were much faster in the mouse. The above rodent species employ two different strategies for the open probability increase by activated G-proteins; the mean open time was shorter in the mouse compared to that in the guinea-pig (15.1 +/- 5.2 msec, n = 8, vs. 80.0 +/- 19.7 msec, n = 9; P < 0.01). Correspondingly, the instantaneous frequency of channel opening was much higher in the mouse (154.1 +/- 18.8 sec(-1) vs. 70.2 +/- 7.3 sec(-1) in the guinea-pig; P < 0.001). These functional differences are discussed based on structural differences found in the corresponding TRPC4 amino acid sequences of the two rodent species, which are mainly clustered in the cytosolic C-terminus of TRPC4 protein.

Psychiatric and neurological disorders are mostly associated with the changes in neural calcium ion signaling pathways required for activity-triggered cellular events. One calcium channel family is the TRP cation channel family, which contains seven subfamilies. Results of recent papers have discovered that calcium ion influx through TRP channels is important. We discuss the latest advances in calcium ion influx through TRP channels in the etiology of psychiatric disorders. Activation of TRPC4, TRPC5, and TRPV1 cation channels in the etiology of psychiatric disorders such as anxiety, fear-associated responses, and depression modulate calcium ion influx. Evidence substantiates that anandamide and its analog (methanandamide) induce an anxiolytic-like effect via CB1 receptors and TRPV1 channels. Intracellular calcium influx induced by oxidative stress has an significant role in the etiology of bipolar disorders (BDs), and studies recently reported the important role of TRP channels such as TRPC3, TRPM2, and TRPV1 in converting oxidant or nitrogen radical signaling to cytosolic calcium ion homeostasis in BDs. The TRPV1 channel also plays a function in morphine tolerance and hyperalgesia. Among psychotropic drugs, amitriptyline and capsazepine seem to have protective effects on psychiatric disorders via the TRP channels. Some drugs such as cocaine and methamphetamine also seem to have an important role in alcohol addiction and substance abuse via activation of the TRPV1 channel. Thus, we explore the relationships between the etiology of psychiatric disorders and TRP channel-regulated mechanisms. Investigation of the TRP channels in psychiatric disorders holds the promise of the development of new drug treatments.