TRPM4 Expression During Postnatal Developmental of Mouse CA1 Pyramidal Neurons

Abstract

TRPM4 is a non-selective cation channel activated by intracellular calcium and permeable to monovalent cations. This channel participates in the control of neuronal firing, neuronal plasticity, and neuronal death. TRPM4 depolarizes dendritic spines and is critical for the induction of NMDA receptor-dependent long-term potentiation in CA1 pyramidal neurons. Despite its functional importance, no subcellular localization or expression during postnatal development has been described in this area. To examine the localization and expression of TRPM4, we performed duplex immunofluorescence and patch-clamp in brain slices at different postnatal ages in C57BL/6J mice. At P0 we found TRPM4 is expressed with a somatic pattern. At P7, P14, and P35, TRPM4 expression extended from the soma to the apical dendrites but was excluded from the axon initial segment. Patch-clamp recordings showed a TRPM4-like current active at the resting membrane potential from P0, which increased throughout the postnatal development. This current was dependent on intracellular Ca2+ (ICAN) and sensitive to 9-phenanthrol (9-Ph). Inhibiting TRPM4 with 9-Ph hyperpolarized the membrane potential at P14 and P35, with no effect in earlier stages. Together, these results show that TRPM4 is expressed in CA1 pyramidal neurons in the soma and apical dendrites and associated with a TRPM4-like current, which depolarizes the neurons. The expression, localization, and function of TRPM4 throughout postnatal development in the CA1 hippocampal may underlie an important mechanism of control of membrane potential and action potential firing during critical periods of neuronal development, particularly during the establishment of circuits.

A glibenclamide-sensitive TRPM4-mediated component of CA1 excitatory postsynaptic potentials appears in experimental autoimmune encephalomyelitis

“…Alternatively, antigenic sites may be masked in tissue, or the antibodies recognize some endogenous protein that is not TRPM4 and is therefore present in both the wild-type and TRPM4-lacking mice. A recent study demonstrated somato-dendritic immunostaining against TRPM4 in CA1 neurons of the hippocampus, however, there was no published validation of these antibodies in Trpm4 –/– tissue 21 .…”

“…In the hippocampus, knock-out of TRPM4 impairs theta-burst induced long-term potentiation (LTP) of synaptic transmission 19 and in cerebellar Purkinje cells, both TRPM4 and TRPM5 contribute to, but are not absolutely required for the depolarization-induced slow current 20 . Recently, CA1 pyramidal neurons have been reported to express TRPM4 along the apical dendrites, accompanied by a TRPM4-dependent inward current 21 . TRPM4 may therefore be synaptically activated in CA1 neurons by calcium entering downstream of NMDA and metabotropic glutamate receptors.…”

Knockdown of the TRPM4 channel alters cardiac electrophysiology and hemodynamics in a sex‐ and age‐dependent manner in mice

“…The dynamic expression of TRPM4 protein may also be related to this time‐dependent cardiac alteration. In mouse CA1 pyramidal neurons the expression of TRPM4 has been shown to increase after birth (Riquelme et al, 2021 ), while it decreases with age in urinary bladder smooth muscle cells (Maxwell et al, 2021 ). Additionally, a cyclic expression of TRPM4 has been shown in female vomeronasal neurons due to the ovarian sex hormone cycle (Eckstein et al, 2020 ).…”

Pharmacological Modulation and (Patho)Physiological Roles of TRPM4 Channel—Part 2: TRPM4 in Health and Disease

“…TRPM4 can contribute to the persistent firing pattern of murine thalamic reticular neurons [105]. In murine CA1 pyramidal neurons, TRPM4 was only expressed on the soma at birth and its expression extended during postnatal development from the soma to the apical dendrites but not to the axon initial segment [106]. A TRPM4-like current was active at the resting membrane potential from birth and increased during development, but 10 µM 9-phenanthrol-induced current inhibition hyperpolarized the membrane potential only at later stages.…”