The Na+-Activated K+ Channel in Cardiac Cells

We compared the determinants of spontaneous activity in explanted neonatal (2-day-old) rat ventricle cells and in reaggregates derived from 15-day-old chick embryos. We studied the beating rate with an optical recording method and the underlying electrical activity with glass microelectrodes using the K current blockers cesium (Cs) and tetraethylammonium, varied Ca concentrations, and the Ca antagonist verapamil. In the rat (i) Cs increased the beating rate that was mediated by an increase in the slope of the diastolic potential, (ii) Ca increased the beating rate dramatically at low and medium concentrations to decrease it again at 8 mM Cao.2This increase in the beating rate was mediated by an increase of the slope of the diastolic depolarization. (iii) The beating rate decreased with verapamil at concentrations between 0.5 and 2.0 μM. The effects of Cs and Ca suggest that an increase in net inward current (block of IK1) underlies the positive chronotropic effect of Cs and that the pacemaker mechanism is determined by a Ca inward current or an IT1 type current modulated by variations of Cai. In the chick reaggregates (i) Cs and tetraethylammonium decreased the beating rate that was mainly brought about by a decrease in the slope of diastolic depolarization. (ii) Ca increased the beating rate but to a lesser degree than in the rat and there was no decrease of the beating rate at higher concentrations. (iii) The increase in the beating rate was not mediated by an increase in the slope of the diastolic potential but mainly by a depolarization of the maximum diastolic potential. (iv) Verapamil inhibited electrogenesis before any change in the diastolic potential was evident. The negative chronotropic effect of Cs and tetraethylammonium is compatible with the notion that a voltage- and time-dependent K current was inhibited and that this current determines the pacemaker. Moreover, the Ca component of the pacemaker mechanism in explanted rat ventricle cells resembles either that of the sinoatrial node or represents triggered activity.Key words: pacemaker mechanism, cultured cardiac cells, K-channel blocker, calcium, verapamil.

Download Full-text

Intracellular Na+ activates a K+ channel in mammalian cardiac cells

Nature ◽

10.1038/309354a0 ◽

1984 ◽

Vol 309 (5966) ◽

pp. 354-356 ◽

Cited By ~ 222

Author(s):

M. Kameyama ◽

M. Kakei ◽

R. Sato ◽

T. Shibasaki ◽

H. Matsuda ◽

...

Keyword(s):

Cardiac Cells ◽

K Channel

Download Full-text

Cardiac ATP-sensitive K+ channels: regulation by intracellular nucleotides and K+ channel-opening drugs

AJP Cell Physiology ◽

10.1152/ajpcell.1995.269.3.c525 ◽

1995 ◽

Vol 269 (3) ◽

pp. C525-C545 ◽

Cited By ~ 203

Author(s):

A. Terzic ◽

A. Jahangir ◽

Y. Kurachi

Keyword(s):

Katp Channel ◽

Molecular Mechanisms ◽

Enzymatic Reaction ◽

Katp Channels ◽

Cardiac Cells ◽

K Channel ◽

Channel Activity ◽

Pharmacological Agents ◽

Channel Opening ◽

Main Regulator

ATP-sensitive K+ (KATP) channels are present at high density in membranes of cardiac cells where they regulate cardiac function during cellular metabolic impairment. KATP channels have been implicated in the shortening of the action potential duration and the cellular loss of K+ that occurs during metabolic inhibition. KATP channels have been associated with the cardioprotective mechanism of ischemia-related preconditioning. Intracellular ATP (ATPi) is the main regulator of KATP channels. ATPi has two functions: 1) to close the channel (ligand function) and 2) in the presence of Mg2+, to maintain the activity of KATP channels (presumably through an enzymatic reaction). KATP channel activity is modulated by intracellular nucleoside diphosphates that antagonize the ATPi-induced inhibition of channel opening or induce KATP channels to open. How nucleotides will affect KATP channels depends on the state of the channel. K+ channel-opening drugs are pharmacological agents that enhance KATP channel activity through different mechanisms and have great potential in the management of cardiovascular conditions. KATP channel activity is also modulated by neurohormones. Adenosine, through the activation of a GTP-binding protein, antagonizes the ATPi-induced channel closure. Understanding the molecular mechanisms that underlie KATP channel regulation should prove essential to further define the function of KATP channels and to elucidate the pharmacological regulation of this channel protein. Since the molecular structure of the KATP channel has now become available, it is anticipated that major progress in the KATP channel field will be achieved.

Download Full-text

Masking of A-type K+ channel in guinea pig cardiac cells by extracellular Ca2+

AJP Cell Physiology ◽

10.1152/ajpcell.1993.264.6.c1434 ◽

1993 ◽

Vol 264 (6) ◽

pp. C1434-C1438 ◽

Cited By ~ 38

Author(s):

M. Inoue ◽

I. Imanaga

Keyword(s):

Guinea Pig ◽

Inhibitory Effect ◽

Cardiac Cells ◽

K Channel ◽

Physiological Conditions ◽

Transient Component ◽

Type K ◽

Outward Currents ◽

Steady State Inactivation ◽

Slope Factor

Removal of extracellular Ca2+ induced transient outward currents (Io) at membrane potentials more positive than 0 mV in the guinea pig cardiac cell. This current reached a peak within a few milliseconds of stimulation, then decreased exponentially. External Cd2+ (0.1 mM) mimicked the inhibitory effect of Ca2+ on Io. Addition of D 600 (1 microM) or quinidine (0.1 mM) in the perfusate produced a reversible suppression, and replacement of internal K+ with tetraethylammonium induced a complete inhibition of Io. The steady-state inactivation of the transient component of Io was expressed by a Boltzmann relation with a half-inactivation voltage of -33.5 mV and a slope factor of 7.5 mV. This transient component was completely or almost completely inhibited by substitution of 4-aminopyridine for external cations. We conclude that in guinea pig cardiac cells, extracellular Ca2+ at physiological concentrations is masking the activity of an A-type K+ channel. This finding implies that even should a channel gene or transcript be identified using molecular biological techniques, the channel may not necessarily function under physiological conditions.

Download Full-text

Confocal imaging of calcium in intact ventricular muscle provides a new view of excitation-contraction coupling

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100166154 ◽

1996 ◽

Vol 54 ◽

pp. 738-739

Author(s):

W.G. Wier

Keyword(s):

Local Control ◽

Cardiac Tissue ◽

Cell Function ◽

Isolated Heart ◽

Cardiac Cells ◽

Confocal Imaging ◽

Ion Concentration ◽

Heart Cell ◽

Free Calcium ◽

Heart Cells

A fundamentally new understanding of cardiac excitation-contraction (E-C) coupling is being developed from recent experimental work using confocal microscopy of single isolated heart cells. In particular, the transient change in intracellular free calcium ion concentration ([Ca2+]i transient) that activates muscle contraction is now viewed as resulting from the spatial and temporal summation of small (∼ 8 μm3), subcellular, stereotyped ‘local [Ca2+]i-transients' or, as they have been called, ‘calcium sparks'. This new understanding may be called ‘local control of E-C coupling'. The relevance to normal heart cell function of ‘local control, theory and the recent confocal data on spontaneous Ca2+ ‘sparks', and on electrically evoked local [Ca2+]i-transients has been unknown however, because the previous studies were all conducted on slack, internally perfused, single, enzymatically dissociated cardiac cells, at room temperature, usually with Cs+ replacing K+, and often in the presence of Ca2-channel blockers. The present work was undertaken to establish whether or not the concepts derived from these studies are in fact relevant to normal cardiac tissue under physiological conditions, by attempting to record local [Ca2+]i-transients, sparks (and Ca2+ waves) in intact, multi-cellular cardiac tissue.

Download Full-text