Changes in osmolality modulate voltage-gated calcium channels in trigeminal ganglion neurons

Abstract

Voltage-gated calcium channels (VGCCs) participate in many important physiological functions. However whether VGCCs are modulated by changes of osmolarity and involve in anisotonicityinduced nociception are still unknown. For this reason by using whole cell patch clamp techniques in rat and mouse trigeminal ganglion (TG) neurons we tested the effects of hypo and hypertonicity on VGCCs. We found that high voltage-gated calcium current (I HVA ) was inhibited by both hypo and hypertonicity. In rat TG neurons, the inhibition by hypotonicity was mimicked by Transient Receptor Potential Vanilloid 4 receptor (TRPV4) activator but hypotonicity did not exhibit inhibition in TRPV4 −/− mice TG neurons. Concerning the downstream signaling pathways, antagonism of PKG pathway selectively reduced the hypotonicity-induced inhibition, whereas inhibition of PLC-and PI3K-mediated pathways selectively reduced the inhibition produced by hypertonicity. In summary, although the effects of hypo-and hypertonicity show similar phenotype, receptor and intracellular signaling pathways were selective for hypo-versus hypertonicity induced inhibition of I HVA .

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…TRPV4 is highly expressed in bronchial smooth muscle, where it is thought to contribute to Ca 2+ mobilization (Jia et al, 2004). TRPV4 was reported to be activated (Chen et al, 2008a), or at least potentiated (Güler et al, 2002), by hypoosmolar solutions. Because individuals with asthma produce copious amounts of airway secretions with low osmolarity, one attractive hypothesis for further exploration is that activation of TRPV4 by hypo-osmolar secretions in bronchial smooth muscle is a major cause of bronchoconstriction in these patients (see Liedtke and Simon, 2004).…”

International Union of Basic and Clinical Pharmacology. LXXVI. Current Progress in the Mammalian TRP Ion Channel Family

“…Like TRPV1, TRPV4 is modulated by CaM and ATP, C-terminal CaM binding potentiating the current (Strotmann et al, 2003) and Ca 2ϩ -dependent CaM binding to the N terminus desensitizing the current (Rosenbaum et al, 2004;Lishko et al, 2007). A variety of kinases also seem to modulate its activity (Gao et al, 2003;Chen et al, 2008a;Fan et al, 2009;Wegierski et al, 2009).…”

Transient Receptor Potential Vanilloid 4-Induced Modulation of Voltage-Gated Sodium Channels in Hippocampal Neurons

“…It has been reported that TRPV4 is involved in the modulation of VSGCs (TTX-R and TTX-S) in TG neurons through the regulation of various intracellular signaling pathways [15,16]. In addition to VGSCs, voltage-gated potassium and calcium channels, TRPV1, and glutamate receptors are also modulated by TRPV4 activation [9,[17][18][19][20].…”