Transient cytosolic calcium ([Ca²⁺]_cyt) elevation is an ubiquitous denominator of the signaling network when plants are exposed to literally every known abiotic and biotic stress. These stress-induced [Ca²⁺]_cyt elevations vary in magnitude, frequency, and shape, depending on the severity of the stress as well the type of stress experienced. This creates a unique stress-specific calcium “signature” that is then decoded by signal transduction networks. While most published papers have been focused predominantly on the role of Ca²⁺ influx mechanisms to shaping [Ca²⁺]_cyt signatures, restoration of the basal [Ca²⁺]_cyt levels is impossible without both cytosolic Ca²⁺ buffering and efficient Ca²⁺ efflux mechanisms removing excess Ca²⁺ from cytosol, to reload Ca²⁺ stores and to terminate Ca²⁺ signaling. This is the topic of the current review. The molecular identity of two major types of Ca²⁺ efflux systems, Ca²⁺-ATPase pumps and Ca²⁺/H⁺ exchangers, is described, and their regulatory modes are analyzed in detail. The spatial and temporal organization of calcium signaling networks is described, and the importance of existence of intracellular calcium microdomains is discussed. Experimental evidence for the role of Ca²⁺ efflux systems in plant responses to a range of abiotic and biotic factors is summarized. Contribution of Ca²⁺-ATPase pumps and Ca²⁺/H⁺ exchangers in shaping [Ca²⁺]_cyt signatures is then modeled by using a four-component model (plasma- and endo-membrane-based Ca²⁺-permeable channels and efflux systems) taking into account the cytosolic Ca²⁺ buffering. It is concluded that physiologically relevant variations in the activity of Ca²⁺-ATPase pumps and Ca²⁺/H⁺ exchangers are sufficient to fully describe all the reported experimental evidence and determine the shape of [Ca²⁺]_cyt signatures in response to environmental stimuli, emphasizing the crucial role these active efflux systems play in plant adaptive responses to environment.

Many stresses are associated with increased accumulation of reactive oxygen species (ROS) and polyamines (PAs). PAs act as ROS scavengers, but export of putrescine and/or PAs to the apoplast and their catabolization by amine oxidases gives rise to H₂O₂ and other ROS, including hydroxyl radicals (^•OH). PA catabolization-based signalling in apoplast is implemented in plant development and programmed cell death and in plant responses to a variety of biotic and abiotic stresses. Central to ROS signalling is the induction of Ca²⁺ influx across the plasma membrane. Different ion conductances may be activated, depending on ROS, plant species, and tissue. Both H₂O₂ and ^•OH can activate hyperpolarization-activated Ca²⁺-permeable channels. ^•OH is also able to activate both outward K⁺ current and weakly voltage-dependent conductance (ROSIC), with a variable cation-to-anion selectivity and sensitive to a variety of cation and anion channel blockers. Unexpectedly, PAs potentiated ^•OH-induced K⁺ efflux in vivo, as well as ROSIC in isolated protoplasts. This synergistic effect is restricted to the mature root zone and is more pronounced in salt-sensitive cultivars compared with salt-tolerant ones. ROS and PAs suppress the activity of some constitutively expressed K⁺ and non-selective cation channels. In addition, both ^•OH and PAs activate plasma membrane Ca²⁺-ATPase and affect H⁺ pumping. Overall, ^•OH and PAs may provoke a substantial remodelling of cation and anion conductance at the plasma membrane and affect Ca²⁺ signalling.

Polyamines are unique polycationic metabolites, controlling a variety of vital functions in plants, including growth and stress responses. Over the last two decades a bulk of data was accumulated providing explicit evidence that polyamines play an essential role in regulating plant membrane transport. The most straightforward example is a blockage of the two major vacuolar cation channels, namely slow (SV) and fast (FV) activating ones, by the micromolar concentrations of polyamines. This effect is direct and fully reversible, with a potency descending in a sequence Spm4+>Spd3+ >Put2+. On the contrary, effects of polyamines on the plasma membrane cation and K+-selective channels are hardly dependent on polyamine species, display a relatively low affinity, and are likely to be indirect. Polyamines also affect vacuolar and plasma membrane H+ pumps and Ca2+ pump of the plasma membrane. On the other hand, catabolisation of polyamines generates H2O2 and other reactive oxygen species, including hydroxyl radicals. Export of polyamines to the apoplast and their oxidation there by available amine oxidases results in the induction of a novel ion conductance and confers Ca2+ influx across the plasma membrane. This mechanism, initially established for plant responses to pathogen attack (including a hypersensitive response), has been recently shown to mediate plant responses to a variety of abiotic stresses. In this review we summarize the effects of polyamines and their catabolites on cation transport in plants and discuss the implications of these effects for ion homeostasis, signaling, and plant adaptive responses to environment.

Reactive oxygen species (ROS) are integral components of the plant adaptive responses to environment. Importantly, ROS affect the intracellular Ca2+ dynamics by activating a range of nonselective Ca2+-permeable channels in plasma membrane (PM). Using patch-clamp and noninvasive microelectrode ion flux measuring techniques, we have characterized ionic currents and net K+ and Ca2+ fluxes induced by hydroxyl radicals (OH•) in pea (Pisum sativum) roots. OH•, but not hydrogen peroxide, activated a rapid Ca2+ efflux and a more slowly developing net Ca2+ influx concurrent with a net K+ efflux. In isolated protoplasts, OH• evoked a nonselective current, with a time course and a steady-state magnitude similar to those for a K+ efflux in intact roots. This current displayed a low ionic selectivity and was permeable to Ca2+. Active OH•-induced Ca2+ efflux in roots was suppressed by the PM Ca2+ pump inhibitors eosine yellow and erythrosine B. The cation channel blockers gadolinium, nifedipine, and verapamil and the anionic channel blockers 5-nitro-2(3-phenylpropylamino)-benzoate and niflumate inhibited OH•-induced ionic currents in root protoplasts and K+ efflux and Ca2+ influx in roots. Contrary to expectations, polyamines (PAs) did not inhibit the OH•-induced cation fluxes. The net OH•-induced Ca2+ efflux was largely prolonged in the presence of spermine, and all PAs tested (spermine, spermidine, and putrescine) accelerated and augmented the OH•-induced net K+ efflux from roots. The latter effect was also observed in patch-clamp experiments on root protoplasts. We conclude that PAs interact with ROS to alter intracellular Ca2+ homeostasis by modulating both Ca2+ influx and efflux transport systems at the root cell PM.

Anticancer properties of non-psychoactive cannabinoid cannabidiol (CBD) have been demonstrated on tumors of different histogenesis. Different molecular targets for CBD were proposed, including cannabinoid receptors and some plasma membrane ion channels. Here we have shown that cell lines derived from acute lymphoblastic leukemia of T lineage (T-ALL), but not resting healthy T cells, are highly sensitive to CBD treatment. CBD effect does not depend on cannabinoid receptors or plasma membrane Ca²⁺-permeable channels. Instead, CBD directly targets mitochondria and alters their capacity to handle Ca²⁺. At lethal concentrations, CBD causes mitochondrial Ca²⁺ overload, stable mitochondrial transition pore formation and cell death. Our results suggest that CBD is an attractive candidate to be included into chemotherapeutic protocols for T-ALL treatment.

Summary: Active removal of Na⁺ from the cytosol into the vacuole plays a critical role in salinity tissue tolerance, but another, often neglected component of this trait is Na⁺ retention in vacuoles. This retention is based on an efficient control of Na⁺‐permeable slow‐ and fast‐vacuolar channels that mediate the back‐leak of Na⁺ into cytosol and, if not regulated tightly, could result in a futile cycle. This Tansley insight summarizes our current knowledge of regulation of tonoplast Na⁺‐permeable channels and discusses the energy cost of vacuolar Na⁺ sequestration, under different scenarios. We also report on a phylogenetic and bioinformatic analysis of the plant two‐pore channel family and the difference in its structure and regulation between halophytes and glycophytes, in the context of salinity tolerance.