Hyperpolarizing current

A structurally novel series of substituted 10//-benzo[4,5]furo[3,2- ]indole-l-carboxylic acids 504-507 was prepared and shown to possess potent, bladder-selective smooth muscle relaxant properties and thus is potentially useful for the treatment of urge urinary incontinence. Electrophysiological studies using rat detrusor myocytes have demonstrated that prototype compound 8 produces a significant increase in hyperpolarizing current, which is iberiotoxin (IbTx)-reversed, thus consistent with activation of the large-conductance Ca -activated potassium channel (BKca) <2001BML2093>. 

This variability in temporal characteristics also exists across insect species. For instance, in cockroaches certain ORNs show onset and offset of firing correlated with stimulation (Getz and Akers, 1997) whereas some ORNs in T sensilla of moths continue firing after the end of odor delivery (Anderson et al., 1995). The occurrence of excitatory and inhibitory responses in single ORNs (depolarization and hyperpolarization, respectively) was noted by Boeckh (1967) in a beetle and a blowfly and is well documented in lobsters (Ache and Zhainazarov, 1995). Inhibitory responses were also observed in patch-clamp recordings of Drosophila antennal ORNs (Dubin and Harris, 1997). Hyperpolarizing currents were due to a decrease in an outward Cl current. 

For dye injection, tips are backfilled with a solution of 5 mg/ml carboxyfluorescein that has been dissolved at pH 10 and then adjusted to pH 7.4 in 0.2 M KCl (Goodall and Johnson, 1984), while the shaft is filled with 0.2 M KCl. Dye and current injection are performed using 500 msec hyperpolarizing current pulses, with 500 msec intervals, at a magnitude of 2 nA (Goodall and Maro, 1986). 

In a companion paper, MacVicar and Dudek (1980a) have recorded simultaneously on 88 occasions from pairs of CAS cells lying less than 200 xm apart. However, even though on 10 occasions spikes in one cell resulted in inhibition of the other and in five excitations, they do not mention electronic coupling. Indeed, on all five occasions, the excitation was strictly unidirectional and on two the amplitude of the underlying epsp in the postsynaptic cell could be increased in amplitude by the injection of hyperpolarizing current. 

Fig. 18. Intradendritic recordings from a CAl pyramidal cell. (A) Postsynaptic activities evoked by striatum radiatum stimulation. Control dendritic spike (in trace 1) was recorded in penetration 350 p,m away from the cell-body layer. In traces 2-4, hyperpolarizing currents applied during orthodromic stimulation blocked the spike in steps and uncovered an excitatory postsynaptic potential (trace 4). (B) Spontaneous (trace 1) and directly evoked burst (trace 2) in the same dendrite as in (A). TTX-resistant activity of this dendrite is shown in trace 3. Whereas short-duration (20 msec) depolarizing pulses could evoke depolarizations that triggered bursts (trace 2), excitatory postsynaptic potential of comparable duration that produced even larger depolarizations only evoked a spike [cf. trace 1 in (A) and trace 2 in (B)]. Membrane potential 60 mV. Lower trace is the current monitor. (From Wong et ai, 1979.)...

Fig. 20. SA spikes depolarizing after-potentials. Hyperpolarizing current injected through the recording electrode enhances the amplitude of the depolarizing after-potential until all-or-none SA spikes evoked by the after-potential initiate full-blown action potentials.

Fig. 27. Intracellular recordings from a granule cell in the hippocampal slice to show the response to the iontophoretic application of GABA. (A) Voltage record made on moving film to show the way in which an intracellular injection of a depolarizing ramp of current is used to test the cell s excitability. Every alternate second a hyperpolarizing current pulse is used to measure the input resistance. As shown more clearly in the single shots in (B) and (C), the application of GABA inhibited the spike discharge evoked by the ramp, caused a substantial decrease in the input resistance, and produced a small depolarization with respect to resting membrane potential [dotted line in (B)]. (From Assaf et ai, 1981.)...

Segal s (1980) attempts to prove the involvement of ions in the hyperpolarization evoked by 5-HT were only partially successful, since only partial reversal of the response was achieved by passing hyperpolarizing current through the electrode. However, on two cells, only a minimal hyperpolarization was evoked by 5-HT when the cells were partially depolarized by raising the external concentration in the external media to 10 mM. However, the addition of 10 mM TEA to the medium also failed to block the hyperpolarization evoked by 5-HT, even though the concentration was sufficient to increase the membrane resistance and cause substantial spike widening. 

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