= ОБЗОРЫ
УДК 577.3
ELECTRICAL EXCITABILITY OF TASTE CELLS. MECHANISMS AND POSSIBLE PHYSIOLOGICAL SIGNIFICANCE
© 2012 R. A. Romanov, O. A. Rogachevskaja, M. F. Bystrova, S. S. Kolesnikov*
Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow obl., 142290 Russia;
*e-mail: staskolesnikov@yahoo.com Received 23.08.2011
Neuronal, muscle and some endocrine cells are electrically excitable. While in muscle and endocrine cells AP stimulates and synchronizes intracellular processes, neurons employ action potentials (APs) to govern discontinuous synapses located distantly. Meanwhile, such axonless sensory cells as photoreceptors and hair cells exemplify afferent output, which is not driven by APs; instead, gradual receptor potentials elicited by sensory stimuli control the release of afferent neurotransmitter glutamate. Mammalian taste cells of the type II and type III are electrically excitable and respond to stimulation by firing APs. Since taste cells also have no axons, physiological significance of the electrical excitability for taste transduction and encoding sensory information is unclear. Perhaps, AP facilitates transmitter release, ATP in type II cells and 5-HT in type III cells, although via different mechanisms. The ATP release is mediated by connexin hemichannels, does not require a Ca2+ trigger, and largely gated by membrane voltage. 5-HT secretion is driven by intracellular Ca2+ and involves VG Ca2+ channels. Here, we discuss ionic mechanisms of excitability of taste cells and speculate on a likely role of APs in mediating their afferent output.
Keywords: taste cell, electrical excitability, afferent neurotransmission, ATP, serotonin.
Electrical excitability is a fundamental property of neuronal and muscle cells and certain other cells, which generate all-or-none electrical signals, action potentials (APs), upon external stimulation of sufficient strength. In neurons, the elongated axon serves to transmit information in the form of APs over a long distance in a non-decremental manner. When the AP comes in the synaptic terminal, one triggers and shapes neurotransmitter release. The AP stimulates and synchronizes intracellular processes in muscle and endocrine cells. Electrical excitability is also inherent in taste cells, albeit they have no axons and are epithelial in nature [1].
Pioneer intracellular recordings from taste buds of the salamander Necturus [2] provided the first evidence for electrical excitability of taste cells. It is now well documented that in vertebrates, taste cells generate APs not only on electrical stimulation, but also in response to apically applied chemical stimuli [3—7]. To generate APs, taste cells should express appropriate ion channels, such as voltage-gated (VG) Na+ and K+ channels, and have a high input resistance at rest, thus allowing a small depolarizing ionic current to impact membrane voltage. As demonstrated in earlier studies, the needed membrane properties are indeed characteristic of taste cells [8, 9]. Since the detailed analysis of ion permeability of the taste cell plasma membrane is beyond the scope of the present work, ion channels are considered here in two specific aspects: in context
of functional identification of taste cells and in relat-edness to their excitability and afferent output.
Note that vertebrate photoreceptors and hair cells in the Corty organ, other axonless sensory cells, do not generate APs on sensory stimuli. This questions why taste cells are electrically excitable. The likely possibility is that despite the absence of axons, taste cells need APs to control afferent output. For the further discussion, we provide below a brief overview of mechanisms mediating neurotransmitter discharge.
SYNAPTIC TRANSMISSION
Discontinuous and graded synapses
Apart from commonly occurring synaptic transmission that involves discontinuous transmitter release driven by presynaptic APs, there are graded-po-tential synapses [10]. Vertebrate photoreceptors and their second order neurons (bipolar cells), auditory and vestibular hair cells respond to external stimulation with graded potentials [11]. These cells have short or no axons and a characteristic synaptic topology adjusted to transform graded presynaptic signals into tonic transmitter release. Their so-called ribbon synapses recognized by synaptic 'ribbon', a specific pre-synaptic organelle, invariably use glutamate as the principle transmitter [11]. The advantage of APs is a reliable transmission of information over long distances, while graded potentials, which can only operate over a short distance, allow for a higher bandwidth and
information capacity [10], the feature relevant for sensory information processing. For example, blowfly photoreceptors gradually transmit information through chemical synapses to large monopolar cells with the rate of nearly 2000 bits/s [12], while for spiking neurons, estimates of the maximal rate of neurotransmission give at least fivefold lower values [13—15]. The primary processes that mediate transmission in both spiking and graded synapses are basically similar.
Ca2+-dependent exocytosis
The synaptic transmission in discontinuous synapses occurs when AP stimulates VG Ca2+ channels in a presynaptic terminal. A brief Ca2+ transient initiates fusion of neurotransmitter-filled synaptic vesicle with the membrane in the active zone, a specialized region where synaptic vesicles dock, fuse and release neu-rotransmitter into the synaptic cleft. After exocytosis, synaptic vesicles undergo endocytosis, recycling and refilling with neurotransmitters for a new round of exocytosis [16]. The principle Ca2+-dependent mechanism, which couples AP to the discontinuous transmitter release, is well detailed (reviewed in [17, 18]). During the initial depolarizing phase of AP VG Ca2+ channels, primarily of P/Q- and N-type [19—21], open rapidly (for ~ 0.1 ms) but transport a small Ca2+ current since at high positive membrane voltage largely settled by open VG Na+ channels, an electrochemical driving force of Ca2+ influx is low. As soon as the repo-larizing phase of AP befalls, Ca2+ influx rises by several-fold due to a strong increase in the electrochemical gradient of Ca2+ ions. However, in certain synapses, vesicular exocytosis may virtually be a one-stage process, since substantial and quick Ca2+ entry may take place at the moment of the AP peak [22, 23]. Presumably, fast K+ channels preclude too high depolarization of the plasma membrane by VG Na+ channels, thereby retaining high enough driving force for Ca2+ influx [24].
Calcium-dependent exocytosis at ribbon synapses involves largely L-type Ca2+ channels [10, 11]. External Ca2+ enters the synaptic terminal and stimulates fusion machinery [25] with high cooperativity, as is the case with CNS synapses [19, 26, 27]. In ribbon synapses of hair cells and retinal bipolar cells, vesicular neurotransmitter secretion is steeply, with the Hill coefficient of up to 5, dependent on free cytosolic Ca2+ [28, 29]. Glutamate release from a bipolar cell terminal occurs with a physiologically relevant rate only upon high (20—50 ^M) Ca2+ transients [30]. Photoreceptor synapses operate in a different manner: vesicular exocytosis is stimulated at a lower micromolar level of intracellular Ca2+ [31, 32], while exocytosis rate is nearly a linear function of Ca2+ concentration [32—34].
Nonconventional mechanisms
In addition to quantal synaptic signals mediated by the vesicular mechanism, unconventional neurotrans-
mitter release can originate diffusion signals. Presumably emanating from the reversal of transporters, non-vesicular release of neurotransmitters has been demonstrated for several cellular preparations [35—38]. Reportedly, neurons and glial cells can release GABA, the main inhibitory neurotransmitter, using nonvesicular mechanisms [39]. Several different release pathways are characteristic of the neurotransmit-ter/neuromodulator ATP, including exocytosis, the ABC transporter, and a number ofATP-permeable ion channels [40-43].
CELL POPULATION IN THE MAMMALIAN TASTE BUD
The mammalian taste bud is a tight aggregate of several dozens of elongated taste cells and few rounded basal cells. Taste cells undergo continuous renewal throughout life, with the life span of 10-14 days on average, developing from a population of basal cell progenitors [1, 44-46]. In line with the morphological classification, there are three core subtypes (type I, II, and III) of taste cells [47]. Cells distinguished by their morphology are also different in their molecular and functional features.
Type II cells are commonly considered as primary chemosensory cells: they express two structurally distant families of G-protein coupled receptors (GPCRs), T1R and T2R, and downstream signaling effectors for bitter, sweet, and umami taste. Three closely related GPCRs from the T1R family compose at least two dimeric receptors. The heterodimer of T1R2 and T1R3 functions as a promiscuous sweet receptor; T1R1 and T1R3 form a broadly turned L-ami-no acid sensor. The T2R family includes nearly 30 GPCRs recognizing bitter ligands. Although sweet-, umami- and bitter-sensitive taste cells represent separate subpopulations within the type II subgroup, they employ basically the same transduction pathway downstream of molecular receptors and G-proteins, which is associated with activation of phospholipase Cp2, IP3 production and release of Ca2+ from intracellular stores, activation of Ca2+-dependent cation channels TRPM5, membrane depolarization, and release of afferent transmitter, most likely ATP (reviewed in [48-52]). Surprisingly, type II cells do not form classical chemical synapses with afferent nerve endings but utilize ATP-permeable channels for ATP secretion (discussed below).
Taste cells of the type III, also referred to as synap-tic cells, represent the only population of taste bud cells, which form recognizable synapses with afferent nerve
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