Blueprints in Cardiology [USMLE Steps 2,3] by E. Awtry, et al.,

By E. Awtry, et al.,

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Example text

Thus, phosphorylation markedly increases the probability of channel opening with depolarization. An equilibrium would exist between the phosphorylated and dephosphorylated forms of the channel for a given set of conditions. For example, some agents like fluoride ion (<1 mM) increase the force of contraction of the heart and potentiate the Ca2'dependent slow APs and Ca2+influx (Ica), without increasing the level of cyclic AMP (19). Fluoride may act by inhibiting the phosphatase which dephosphorylates the channel protein, thus prolonging the life span of the phosphorylated channel.

In addition, 8Br-CAMP inhibition of the Ca2+-dependentslow APs in mammalian cardiac muscle occurs without a decrease in cAMP levels (39). Thus, it appears that in avian and mammalian ventricular muscle, cGMP inhibits I, directly through a cGMP-mediated phosphorylation (8Br-cGMP is a potent activator of PK-G) of a protein involved in the functioning of the slow Ca2+channels (Fig. I ) . 14 Nicholas Sperelakis VII. Protein Kinase G Inhibition When PK-G (G-kinase, 25 nM) is added to the patch pipette for diffusion into the cell during whole-cell voltage clamp, it was found that basal I,, is inhibited markedly and rapidly, maximum inhibition being reached within 2-3 min (Figs.

A greater density of available Ca2+ channels increases Ca2+influx and inward Ca2+slow current (Ica) during the AP, and so increases the force of contraction of the heart. Phosphorylation by cGMP-dependent protein kinase (PK-G) depresses the activity of the slow Ca2+channels (1). II. Types of Calcium Channels Five different subtypes of voltage-dependent Ca2+ channels have been described for nerve and muscle cells (Table I). Two of these subtypes are known as L-type (or long-lasting or kinetically slow) and T-type (or transient or kinetically fast) (2).

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