Impact of Mammalian Two-Pore Channel Inhibitors on Long-Distance Electrical Signals in the Characean Macroalga Nitellopsis obtusa and the Early Terrestrial Liverwort Marchantia polymorpha

Abstract

Inhibitors of human two-pore channels (TPC1 and TPC2), i.e., verapamil, tetrandrine, and NED-19, are promising medicines used in treatment of serious diseases. In the present study, the impact of these substances on action potentials (APs) and vacuolar channel activity was examined in the aquatic characean algae Nitellopsis obtusa and in the terrestrial liverwort Marchantia polymorpha. In both plant species, verapamil (20–300 µM) caused reduction of AP amplitudes, indicating impaired Ca2+ transport. In N. obtusa, it depolarized the AP excitation threshold and resting potential and prolonged AP duration. In isolated vacuoles of M. polymorpha, verapamil caused a reduction of the open probability of slow vacuolar SV/TPC channels but had almost no effect on K+ channels in the tonoplast of N. obtusa. In both species, tetrandrine (20–100 µM) evoked a pleiotropic effect: reduction of resting potential and AP amplitudes and prolongation of AP repolarization phases, especially in M. polymorpha, but it did not alter vacuolar SV/TPC activity. NED-19 (75 µM) caused both specific and unspecific effects on N. obtusa APs. In M. polymorpha, NED-19 increased the duration of repolarization. However, no inhibition of SV/TPC channels was observed in Marchantia vacuoles, but an increase in open probability and channel flickering. The results indicate an effect on Ca2+ -permeable channels governing plant excitation.

Electrical Signals, Plant Tolerance to Actions of Stressors, and Programmed Cell Death: Is Interaction Possible?

“…An AP is a short-term depolarization spike including two phases (depolarization and repolarization) [ 28 , 35 , 77 , 78 ] which is induced by non-damaging irritations (e.g., electrical current [ 79 , 80 , 81 , 82 , 83 ], cooling [ 41 , 79 , 84 ], touch [ 85 , 86 , 87 ], initiation or termination of illumination [ 88 , 89 ]). The generation of an AP is in accordance with the “all-or-none law” [ 8 , 28 , 35 ]; it is a self-propagating signal with typical velocities ranging from 1 mm s −1 to 10 cm s −1 in different plants [ 8 , 38 , 77 , 80 ].…”

Broadening the definition of a nervous system to better understand the evolution of plants and animals

“… 133 A recent study in Nitellopsis obtusa and Marchantia polymorpha has shown that inhibitors of human two-pore channels alter resting potential, action potential amplitudes and the duration of action potential repolarization by affecting channels. 134 In addition to having a short-lasting depolarisation of the action potential, animals and plants both have signals based on prolonged depolarisation. In animals, a prolonged depolarisation signal is the plateau potential, 135 , 136 and in plants it is the variation potential.…”

“… 133 A recent study in Nitellopsis obtusa and Marchantia polymorpha has shown that inhibitors of human two-pore channels alter resting potential, action potential amplitudes and the duration of action potential repolarization by affecting channels. 134 …”

TPC1-Type Channels in Physcomitrium patens: Interaction between EF-Hands and Ca2+

“…In Arabidopsis, AtTPC1 forms the slow vacuolar (SV) channel [3]. Nevertheless, SV channels have also been characterized in non-vascular mosses and liverworts [39][40][41][42]. Marchantia polymorpha is a representative of liverworts, which are regarded as pioneer plants that colonized the land around 500 million years ago.…”