Cells hyperpolarization

Another way to increase the entry of Ca2+ across the plasma membrane is to hyperpolarize the plasma membrane by elevating active ion transport. Fischer et al. [130] demonstrated that hyperpolarization of colonic epithelial cells (HT-29) with carbachol elevates the intracellular levels of Ca2+, [Ca2+]i while depolarization with gramicidin D or elevation of K+ in the bathing fluid reverses it. Treatment with 0.1 mM carbachol produced a spontaneous increase in [Ca2+]i from 63 nM to 901 nM. This lasted for about 3 min, beyond which a plateau level of 309 nM was maintained. While the initial Ca2+ transient was present in Ca2+-free medium containing 0.1 mM EGTA, the plateau phase was suppressed to baseline levels, suggesting that carbachol initially releases Ca2+ from the intracellular stores and subsequently increases the Ca2+ entry across the plasma membrane. In cells hyperpolarized with carbachol, induction of depolarization by ele-... 

Salter DM, Wallace WH, Robb JE, Caldwel H, Wright MO. Human bone cell hyperpolarization response to cyclical mechanical strain is mediated by an interleukin-lbeta autocrine/paracrine loop. J Bone Miner Res. 2000 15 1746-1755. 

In pituitary adenoma cells, dopamine was found to activate K+ currents through D2 type receptor, leading to cell hyperpolarization (Israel et al., 1985). Similar effects have been described in lactotroph and melanotroph cells in the anterior pituitary as well as in the mesencephalic neurons in the CNS (Israel et al., 1985 Lacey et al., 1988 Greif et al., 1995). The K+ current-induced hyperpolarization appears to underlie the inhibition of DA release mediated by D2 autoreceptors in dopamine neurons and of prolactin release in lactotroph cells. In particular, the blockade of K+ channel by 4-aminopyridine or tetramethylammonium abolished the inhibitory effect of D2 agonists on DA release (Bowyer and Weiner, 1989 Cass and Zahniser, 1991 Tang et al., 1994a). 

D2R activation also increases outward potassium currents, leading to cell hyperpolarization in a number of preparations (Castelletti et al., 1989 Vallar et al., 1990 Einhorn et al., 1991 Lledo et al., 1992 Kitai and Surmeier, 1993). Although the effect on potassium channels has been established as G-protein-dependent, the a-subunit involved appears to differ with the tissue used, as in the pituitary Gai3 plays an essential role (Baertschi et al., 1992 Lledo et al., 1992), whereas Ga0 is involved in preparations from the rat mesencephalon (Liu et al., 1994a). 

Neurotransmitters affect receptors in two basic ways. Some bind to receptors which are said to have ionic effects. These receptors, when activated, operate to open tiny pores (ion-channels), allowing electrically charged particles (ions) to enter the nerve cell. When numerous ionic receptors are activated, this can result in either an excitation of the nerve cell (action potential) or, conversely, a calming of the nerve cell (hyperpolarization, which makes it less likely that the cell will fire). Excitation or inhibition depends on which specific type of channel is activated. This phenomenon is responsible for eliciting immediate and transient changes in neuronal excitability (for example, this occurs when a motor neuron is activated and there is corresponding activation of a muscle, or when sensory events are perceived). 

Figure 9. Fading of the mossy fiber-evoked inhibitory postsynaptic potentials recorded with the cell hyperpolarized to the reversal potential of IPSPb after stimulation at 5 Hz. (Reproduced with permission of the principal investigator and editor of [64]).

Fig. 40. D-Ala -Met-enkephalin (D, ALA) is not a GABA antagonist. The upper traces show the response to orthodromic stimulation (Ortho) and to an iontophoretic GABA pulse (80 nA) applied to the apical dendrites and recorded from the soma of a pyramidal cell. The lower records were obtained 5 min after switching to a 5 xM D.ALA-containing solution. The cell hyperpolarized 3 mV, resulting in a slight increase in the GABA responses. The orthodromic response is markedly curtailed. The bathing medium contained lO"" M pentobarbital. The membrane potential was -52 mV. The recording electrode was filled with 3 M KCl. (From Nicoll et ai, 1980.)...

In the following, the cardiac action potential is explained (Fig. 1) An action potential is initiated by depolarization of the plasma membrane due to the pacemaker current (If) (carried by K+ and Na+, which can be modulated by acetylcholine and by adenosine) modulated by effects of sympathetic innervation and (3-adrenergic activation of Ca2+-influx as well as by acetylcholine- or adenosine-dependent K+-channels [in sinus nodal and atrioventricular nodal cells] or to dqjolarization of the neighbouring cell. Depolarization opens the fast Na+ channel resulting in a fast depolarization (phase 0 ofthe action potential). These channels then inactivate and can only be activated if the membrane is hyperpolarized... 

The disruption of C1C-2 in mice leads to male infertility, blindness, and leukodystrophy, and was attributed to defective extracellular ion homeostasis in narrow clefts. C1C-2 yields currents that slowly activate upon hyperpolarization. It is also activated by cell swelling and by extracellular acidification. Structural determinants that are essential for these types of activation were identified by mutagenesis. There is a report that C1C-2 might be mutated in human epilepsy, but this has not been confirmed in fiuther studies. 

Inward Rectifier K+ Channels. Figure 2 High [K+] inside cells relative to outside results in normal rectification, whereby outward (positive by convention) potassium currents (/) when cells are depolarized (is positive relative to EK), are biggerthan inward (negative) currents at hyperpolarized (negative) voltages. Inward or anomalous rectifiers show strong or weak inward rectification whereby outward currents are smaller than inward currents. 

And we believe that this fact, only recently shown by Allan North s group, is that they cause an increase in potassium conductance and as a consequence hyperpolarization of the cell body. 

ANSWER That is Lacey et al., Allan North s group. It was published in the Journal of Physiology last year. It was also an abstract in the Society 2 years ago. It is the consequence of that application of the agonists, recording intracellularly in the slice of the dopamine neuron. He gets the same thing by virtue of application of norepinephrine agonists to noradrene-gic slice preparation. That is a conventional way to create a hyperpolarization of the cell, to increase the potassium conductance, and so forth. 

QUESTION Do you think it is necessary to have an intact cell to have this hyperpolarization ... 

Salicylic acid depolarized PD In epidermal cells of oat roots also. At pH 4.5, 500 pM salicylic acid caused a transient hyperpolarization followed by a dramatic depolarization to about -45 mV (Figure 2). Removal of salicylic acid produced a transient, partial repolarization. At pH 6.5, salicylic acid did not affect PD. These results with different pH s are consistent with the Influence of salicylic acid on K+ absorption in oat roots (32). 

Other lipophilic weak acids have been shown to alter PD in plant cells. Benzoic and butyric acids (1 PM) rapidly depolarized the PD In oat coleoptile cells at pH 6.0 to about -100 mV (43). Higher concentrations (10 mM) of butyrate produced hyperpolarization. Butyrate also hyperpolarized apical cortical cells of maize roots... 

In cells of the fungus Neurospora crassa, 5 mM butyrate (pH 5.8) produced a transient hyperpolarization followed by depolarization... 

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