After-hyperpolarization promotes the firing of mitral cells through a voltage dependent modification of action potential threshold

In the olfactory bulb (OB), mitral cells (MCs) display a spontaneous firing that is characterized by bursts of action potentials intermixed with silent periods. Burst firing frequency and duration are heterogeneous among MCs and increase with membrane depolarization. By using patch clamp recording on rat slices, we dissected out the intrinsic properties responsible of this activity. We showed that the threshold of action potential (AP) generation dynamically changes as a function of the trajectory of the membrane potential; becoming more negative when the membrane was hyperpolarized and having a recovering rate, inversely proportional to the membrane repolarization rate. Such variations appeared to be produced by changes in the inactivation state of voltage dependent Na+ channels. Thus, the modification AP threshold favours the initiation of the burst following hyperpolarizing event such as negative membrane oscillations or inhibitory transmission. After the first AP, the following afterhyperpolarization (AHP) brought the threshold just below the membrane resting potential or within membrane oscillations and, as a consequence, the threshold was exceeded during the fast repolarization component of the AHP. In this way the fast AHP acts as a regenerative mechanism that sustains the firing. Bursts were stopped by the development of a slow repolarization component of the AHP. The AHP characteristics appeared as determining the bursting properties; AHP with larger amplitudes and faster repolarizations being associated with longer and higher frequency bursts. Thus, the increase of bursts length and frequency upon membrane depolarization would be attributable to the modifications of the AHP and of Na+ channels inactivation.

Functional Pre- and Postsynaptic Changes between the Retinohypothalamic Tract and Suprachiasmatic Nucleus during Rat Postnatal Development

The suprachiasmatic nucleus (SCN) is the main brain clock in mammals. The SCN synchronizes to the light-dark cycle through the retinohypothalamic tract (RHT). RHT axons release glutamate to activate AMPA-kainate and N-methyl-D-aspartate (NMDA) postsynaptic receptors in ventral SCN neurons. Stimulation of SCN NMDA receptors is necessary for the activation of the signaling cascades that govern the advances and delays of phase. To our knowledge, no research has been performed to analyze the functional synaptic modifications occurring during postnatal development that prepare the circadian system for a proper synchronization to light at adult ages. Here, we studied the pre- and postsynaptic developmental changes between the unmyelinated RHT-SCN connections. Spontaneous NMDA excitatory postsynaptic currents (EPSCs) were greater in amplitude and frequency at postnatal day 34 (P34) than at P8. Similarly, both quantal EPSCs (miniature NMDA and evoked quantal AMPA-kainate) showed a development-dependent increase at analyzed stages, P3-5, P7-9, and P13-18. Moreover, the electrically evoked NMDA and AMPA-kainate components were augmented with age, although the increment was larger for the latter, and the membrane resting potential was more depolarized at early postnatal ages. Finally, the short-term synaptic plasticity was significantly modified during postnatal development as was the estimated number of quanta released and the initial release probability. All of these synaptic modifications in the unmyelinated RHT-SCN synapses suggest that synchronization to light at adult ages requires developmental changes similar to those that occur in myelinated fast communication systems.

Potassium homeostasis

The equilibrium between the concentration of K+ in the extracellular space (low) and the intracellular compartment (high) is crucial for maintaining the electrical properties of excitable and non-excitable cells, because it determines the membrane resting potential. The high intracellular concentration of K+ (120–140 mmol/L) also contributes to the intracellular osmolarity, a determinant of cell volume. It is therefore crucial to finely tune both extracellular and intracellular K+ concentrations. There is a coordinated regulation between processes/mechanisms that store/release K+ from internal stores (internal balance) and those that retain/excrete K+ (external balance).

Expression and function of a CP339,818-sensitive K+ current in a subpopulation of putative nociceptive neurons from adult mouse trigeminal ganglia

Trigeminal ganglion (TG) neurons are functionally and morphologically heterogeneous, and the molecular basis of this heterogeneity is still not fully understood. Here we describe experiments showing that a subpopulation of neurons expresses a delayed-rectifying K+ current ( IDRK) with a characteristically high (nanomolar) sensitivity to the dihydroquinoline CP339,818 (CP). Although submicromolar CP has previously been shown to selectively block Kv1.3 and Kv1.4 channels, the CP-sensitive IDRK found in TG neurons could not be associated with either of these two K+ channels. It could neither be associated with Kv2.1 channels homomeric or heteromerically associated with the Kv9.2, Kv9.3, or Kv6.4 subunits, whose block by CP, tested using two-electrode voltage-clamp recordings from Xenopus oocytes, resulted in the low micromolar range, nor to the Kv7 subfamily, given the lack of blocking efficacy of 3 μM XE991. Within the group of multiple-firing neurons considered in this study, the CP-sensitive IDRK was preferentially expressed in a subpopulation showing several nociceptive markers, such as small membrane capacitance, sensitivity to capsaicin, and slow afterhyperpolarization (AHP); in these neurons the CP-sensitive IDRK controls the membrane resting potential, the firing frequency, and the AHP duration. A biophysical study of the CP-sensitive IDRK indicated the presence of two kinetically distinct components: a fast deactivating component having a relatively depolarized steady-state inactivation ( IDRKf) and a slow deactivating component with a more hyperpolarized V1/2 for steady-state inactivation ( IDRKs).

Influence of some new aminophosphonates on electrical properties and stability of plasma membranes of plant cells

The effect of new aminophosphonates, synthesized for potential agricultural application, on membrane potential and electrical conductance of internodal cells of <em>Nitellopsis obtusa</em> and their efficiency in modifying the properties of cucumber (<em>Cucumis sativus</em> cv "Wisconsin") cotyledon membranes was studied. They differed in substituents at the carbon and phosphorus atoms. It was found that the organophosphorous compounds caused depolarization of the membrane resting potential and increased electrical conductance of alga membranes. They also influenced chlorophyll content and efflux of electrolytes from cucumber cotyledons. The most significant effects were observed for the compound with iso-propyl substituents at the P atom. In contrast, the weakest modifier of the studied compounds was the one having phenolic substituents at that atom. The observed changes are most probably the result of direct interaction of aminophosphonates with the lipid phase of the plasma membrane and the induced structural changes in it.

Electrophysiology of oocytes during meiotic maturation and after ovulation in brook trout (Salvelinus fontinalis)

Brook trout oocytes were stripped of their follicular layers and were impaled with both voltage-measuring and current-passing microelectrodes. The membrane resting potential (Vm) was −46 ± 1.2 mV (mean ± SE, n = 50, bath grounded) in control denuded oocytes with an intact germinal vesicle. Vm was reduced to −38 ± 1.8 mV (n = 16) in eggs that had ovulated in vivo. Accompanying the potential drop was a marked increase in membrane resistance (Rm) from 26 ± 1.7 in denuded oocytes to 1640 ± 150 kΩ∙cm2 in ovulated eggs and a reduction in membrane current (Im) from 2380 ± 260 to 25 ± 2.6 nA∙cm2. The increased resistance in ovulated eggs was in part the result of reduced Na+ and K+ membrane conductances; there was no significant change in Cl− conductance. Treatment of denuded oocytes with 17α-20β-dihydroxyprogesterone produced germinal vesicle dissolution; in denuded oocytes that had undergone germinal vesicle dissolution in vitro, Rm increased and Im decreased, comparable at least qualitatively to the changes seen after ovulation in vivo. The results indicate that major electrophysiological changes accompany germinal vesicle dissolution and ovulation in brook trout oocytes.