P Hess

Calcium channel types in cardiac myocytes: modulation by dihydropyridines and beta-adrenergic stimulation

We used the patch clamp technique to record unitary calcium (Ca:2+ ) channel activity in freshly dissociated ventricular myocytes from adult guinea pigs. We found two types of Ca2+ channels with distinct permeation and gating properties and different sensitivity to pharmacological agents. One channel (T-type) requires negative membrane potentials to remove inactivation. It gives rise to a transient mean current and is not affected by dihydropyridines or isoproterenol. The other Ca:2+ channel (L-type) has a larger unitary barium-conductance, activates at more positive potentials and its averaged current decays much more slowly. It shows a distinct gating pattern with different gating modes, the proportion of which is drastically altered by dihydropyridine Ca2 + -channel agonists and antagonists. L-type channel activity is modulated by β-adrenergic stimulation by a mechanism of action which differs from that of dihydropyridine Ca2 + -channel agonists.

Cardiac calcium currents at the level of single channels.

Properties of cardiac Ca channels have come into sharper focus with the advent of single cell preparations and suction pipette recording methods. We briefly summarize our present picture of the gating and permeation properties of the conventional, dihydrophyridine-sensitive type of Ca channel (L-type). Distincitive features of a second type of voltage-gated Ca channel (T-type) are discussed.

Shifts between Modes of Calcium Channel Gating as a Basis for Pharmacological Modulation of Calcium Influx in Cardiac, Neuronal, and Smooth-Muscle-Derived Cells

When Ca2+ channels open in response to an appropriate change in membrane potential, they allow Ca2+ ions to move down their electrochemical gradient into the cytoplasm. This inflow of Ca2+ not only transfers depolarizing charge into excitable cells but also carries a specific message to be decoded by Ca2+ receptor proteins. The signal leads to the initiation of contraction in heart and smooth muscle cells, transmitter release from nerve cell synaptic terminals, hormone secretion by gland cells, and other important cellular responses (Hagiwara and Byerly, 1981, 1983; Reuter, 1983; Tsien, 1983). In linking membrane potential changes to the delivery of a messenger substance, Ca2+ channels perform a function that is vital and possibly unique (Tsien et al., 1983; Hille, 1984).

Chapter 19 Cardiac Calcium Channels: Pore Size and Symmetry of Energy Profile

Publisher Summary This article discusses the studies on L-type Ca channels in heart cells, which are probably the most extensively characterized of the many voltage-dependent Ca channels that have been distinguished in recent years. The two major aims were estimating the radial dimensions of the pore and looking for possible asymmetry of the energy profile along the length of the pore. Calcium channels are among the most interesting examples of the intrinsic membrane proteins that control transmembrane ion flow and cellular function. Present in the surface membranes of all known excitable cells, they open in response to membrane depolarization and allow Ca2+ to move down a steep electrochemical gradient into the cell. The flow of depolarizing charge may help generate action potentials, pacemaker activity, or bursting patterns. The Ca2+ influx may also act as a chemical signal when decoded by calcium-receptor proteins inside the cell. Rises in cytosolic Ca2+ can initiate diverse cellular responses—such as contraction, secretion, activation, and inactivation of ion channels—and can also initiate changes in metabolism and gene expression.