Recovery of the slow inward current from inactivation in the rabbit sinoatrial node

Previous investigations employing multicellular nodal preparations (i.e., mixtures of dominant and subsidiary pacemaker cells) have suggested that the fast transient inward sodium current (iNa) either is not present in dominant pacemaker cells or is present but inactivated at the depolarized take-off potentials that these cells exhibit. In the present study, this question was resolved by voltage clamp analysis of single pacemaker cells isolated from the sinoatrial node and maintained in vitro for 1-3 days. Two types of cells, each with a different morphology, exhibited two modes of electrophysiological behavior. Type I cells (presumably dominant pacemakers) displayed only a tetrodotoxin (TTX)-resistant (but cadmium-sensitive) slow inward current, whereas type II cells (presumably subsidiary pacemakers) exhibited two components of inward current, a TTX-sensitive, fast transient inward current and a TTX-resistant (but cadmium-sensitive) slow inward current. Three other voltage-gated currents, 1) a slowly developing inward current activated by hyperpolarization (if, ih, delta ip), 2) a transient outward current activated by strong depolarization (ito, iA), and 3) a delayed outward current, were recorded in both types of pacemaker cells.

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Inward current of the rabbit sinoatrial node cell

Pflügers Archiv - European Journal of Physiology ◽

10.1007/bf00582205 ◽

1977 ◽

Vol 372 (1) ◽

pp. 43-51 ◽

Cited By ~ 49

Author(s):

A. Noma ◽

K. Yanagihara ◽

H. Irisawa

Keyword(s):

Sinoatrial Node ◽

Inward Current ◽

Sinoatrial Node Cell ◽

Rabbit Sinoatrial Node

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Ionic basis of ryanodine’s negative chronotropic effect on pacemaker cells isolated from the sinoatrial node

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.273.5.h2481 ◽

1997 ◽

Vol 273 (5) ◽

pp. H2481-H2489 ◽

Cited By ~ 19

Author(s):

Jin Li ◽

Jihong Qu ◽

Richard D. Nathan

Keyword(s):

Action Potential ◽

Sinoatrial Node ◽

Slow Inward Current ◽

Spontaneous Firing ◽

Chronotropic Effect ◽

Pacemaker Cells ◽

Acetoxymethyl Ester ◽

Inward Current ◽

Negative Chronotropic Effect ◽

Intracellular Ca

Spontaneous electrical activity and indo 1 fluorescence ratios were recorded simultaneously in cultured pacemaker cells isolated from the rabbit sinoatrial node. Ryanodine (10 μM) reduced the amplitude of action potential-induced intracellular Ca2+([Formula: see text]) transients by 19 ± 3%, increased the time constant for their decay by 51 ± 5%, and slowed spontaneous firing by 32 ± 3%. 1,2-Bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid (BAPTA)-acetoxymethyl ester (AM; 25 μM) inhibited the [Formula: see text] transients and slowed spontaneous firing by 28 ± 4%. Ryanodine did not alter hyperpolarization-activated or time-independent inward current, but it reduced the sum of L- and T-type Ca2+ currents ( I Ca,L and I Ca,T) in both the presence and absence of BAPTA-AM. In contrast, I Ca,L was unchanged by ryanodine. Slow inward current tails, presumed to be Na/Ca exchange current ( I Na/Ca), were abolished by BAPTA or ryanodine. The results suggest that a decrement of I Ca,T, due to reduction of the intracellular Ca2+ concentration or a direct effect of ryanodine on T-type Ca2+channels, contributes to the negative chronotropic effect. Another possibility, based primarily on theory and results in other preparations, is that a reduction of I Na/Ca, as a consequence of the smaller action potential-induced[Formula: see text] transients, contributes to the effect of ryanodine.

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