Coupling hyperpolarization

Membrane depolarization typically results from an increase in Na+ conductance. In addition, mobilization of intracellular Ca2+ from the endoplasmic or sarcoplasmic reticulum and the influx of extracellular Ca2+ appear to be elicited by ACh acting on muscarinic receptors (see Ch. 22). The resulting increase in intracellular free Ca2+ is involved in activation of contractile, metabolic and secretory events. Stimulation of muscarinic receptors has been linked to changes in cyclic nucleotide concentrations. Reductions in cAMP concentrations and increases in cGMP concentrations are typical responses (see Ch. 21). These cyclic nucleotides may facilitate contraction or relaxation, depending on the particular tissue. Inhibitory responses also are associated with membrane hyperpolarization, and this is a consequence of an increased K+ conductance. Increases in K+ conductance may be mediated by a direct receptor linkage to a K+ channel or by increases in intracellular Ca2+, which in turn activate K+ channels. Mechanisms by which muscarinic receptors couple to multiple cellular responses are considered later. 

The SR may contribute to excitation-contraction (EC) coupling in two ways firstly, by the release of Ca2+ for contraction as described above, but secondly by modulating membrane excitability. As will be described elsewhere in this book, the SR is an important mediator of surface membrane ion channel activity, and hence, excitability. Spontaneous Ca2+ release from the SR can activate Ca2+-sensitive ion channels. Both K+ (Kca) and Cl- (Clsmooth muscle cell membrane can be activated by SR Ca2+. If Kca channels are activated there will be a hyperpolarization, as K+ ions leave the cell and spontaneous transient outward currents (STOCs) can be recorded (Carl et al 1996, Nelson Quayle... 

Opioids including morphine acting on metabotrobic pi—opioid receptors produce their inhibitory effect on cellular excitability in part by activation of Gj/0-protein-coupled K+ channels thereby hyperpolarizing the membrane potential (Williams et al., 1982 Han et al.,... 

The 5-HT1A receptors are coupled to potassium and calcium channels. Intracellular current-clamp recordings in slices containing the DR established that the 5-HT-mediated inhibition involved an increase in potassium conductance, which exhibits inward rectification (18,58). This induced a membrane hyperpolarization leading to a decrease in action potential frequency. Similar responses to 5-HT1A receptor activation have been reported in other neuronal types, such as hippocampal pyramidal cells (16,59) or 5-HT neurons of the caudal raphe nuclei (60). 

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