Slow Ca2+ current

FIGURE 10-7 The delay between Ca2+ influx into the nerve terminal and the postsynaptic response is brief. The temporal relationships between the Ca2+ current and the action potential in the nerve terminal and the postsynaptic response in the squid giant synapse are shown. The rapid depolarization (a) and repolarization (b) phases of the action potential are drawn. A major fraction of the synaptic delay results from the slow-opening, voltage-sensitive Ca2+ channels. There is a further delay of approximately 200 is between Ca2+ influx and the postsynaptic response. (With permission from reference [20].)... 

Huag T, Storm JF (2000) Protein kinase A mediates the modulation of the slow Ca2+-dependent K+ current, lsAHP,by the neuropeptides CRF, VIP, and CGRP in hippocampal pyramidal neurons. J Neurophysiol 83 2071-2079 Huang Y, Li X-C, Kandel ER (1994) cAMP contributes to mossy fiber LTP by initiating both a covalently mediated early phase and macromolecular synthesis-dependent late phase. Cell 79 69-79... 

The use of radioactively labelled Ca to monitor changes in the magnitude and duration of the slow Ca + current is also difficult, partly because of the small amounts of Ca2+ that are involved. When considered on a beat to beat basis the Ca + that enters heart muscle cells by way of the slow Ca + current represents less than 2 percent of the total tissue Ca + and if, as seems probable, this small component is rapidly recycled to the exterior its accurate detection during the time course of the action potential presents substantial technical difficulties. 

Quantitatively, the binding of Ca2+ to the glycocalyx is of secondary importance compared to that bound by phospholipid elements. The glycocalyx does play a significant role in the determination of myocardial cell Ca2+ permeability (20, 21). Upon arrival of the appropriate electrical stimulus T ction potential), Ca2+ crosses the sarcolemma and is the principal cation responsible for a current called the "slow inward current" (lsi) (3-2, 22, 23, 24). Calcium is conducted across the sarcolemma through channels or pores which are controlled by the phosphorylation of sarcolemmal and sarcotubular proteins. Cardiac sarcolemma and sarcoplasmic reticulum are phosphorylated by exogenous and endogenous cyclic adenosine 5 -5 - monophosphate (cAMP)-dependent protein kinases (25, ... 

Cardiac Muscle. Calcium inhibitory agents may interfere with excitation-contraction coupling processes in myocardial or vascular smooth muscle cells by a number of mechanisms including l) inhibition of the slow inward current through direct competition for slow channels or interference with the membrane binding of Ca2+ 2) interference with the release... 

Stimulation of the H2 receptor leads to blockade of a Ca2+-dependent K+ current through the small K+ channel, thus causing a spike frequency adaptation (i.e. an accommodation of firing) and slow afterhyperpolarization... 

Slow-channel syndrome. Abnormally long-lived openings of mutant AChR channels result in prolonged endplate currents and potentials, which in turn elicit one or more repetitive muscle action potentials of lower amplitude that decrement. The morphologic consequences stem from prolonged activation of the AChR channel that causes cationic overload of the postsynaptic region - the endplate myopathy - with Ca2+ accumulation, destruction of the junctional folds, nuclear apoptosis, and vacuolar degeneration of the terminal. Some slow-channel mutations in the transmembrane domain of the AChR render the channel leaky by stabilization of the open state, which is populated even in the absence of ACh. Curiously, some slow-channel mutants can be opened by choline even at the concentrations that are normally present in serum. Quinidine, an open-channel blocker of the AchR, is used for therapy. 

---