Characterization of action potential‐triggered [Ca<sup>2+</sup>]<sub>i</sub> transients in single smooth muscle cells of guinea‐pig ileum

British Journal of Pharmacology - Tập 122 Số 3 - Trang 477-486 - 1997
Masanobu Kohda1, S Komori1, Tomonori Unno1, Hidenori Ohashi1
1Laboratory of Pharmacology, Department of Veterinary Science, Faculty of Agriculture, Gifu University, Yanagido 1–1, Gifu 501‐11, Japan

Tóm tắt

To characterize increases in cytosolic free Ca2+ concentration ([Ca2+]i) associated with discharge of action potentials, membrane potential and [Ca2+]i were simultaneously recorded from single smooth muscle cells of guinea‐pig ileum by use of a combination of nystatin‐perforated patch clamp and fura‐2 fluorimetry techniques. A single action potential in response to a depolarizing current pulse elicited a transient rise in [Ca2+]i. When the duration of the current pulse was prolonged, action potentials were repeatedly discharged during the early period of the pulse duration with a progressive decrease in overshoot potential, upstroke rate and repolarization rate. However, such action potentials could each trigger [Ca2+]i transients with an almost constant amplitude. Nicardipine (1 μM) and La3+ (10 μM), blockers of voltage‐dependent Ca2+ channels (VDCCs), abolished both the action potential discharge and the [Ca2+]i transient. Charybdotoxin (ChTX, 300 nM) and tetraethylammonium (TEA, 2 mM), blockers of large conductance Ca2+‐activated K+ channels, decreased the rate of repolarization of action potentials but increased the amplitude of [Ca2+]i transients. Thapsigargin (1 μM), an inhibitor of SR Ca2+‐ATPase, slowed the falling phase and somewhat increased the amplitude, of action potential‐triggered [Ca2+]i transients without affecting action potentials. In addition, in voltage‐clamped cells, the drug had little effect on the voltage step‐evoked Ca2+ current but exerted a similar effect on its concomitant rise in [Ca2+]i to that on the action potential‐triggered [Ca2+]i transient. Similar action potential‐triggered [Ca2+]i transients were induced by brief exposures to high‐K+ solution. They were not decreased, but rather increased, after depletion of intracellular Ca2+ stores by a combination of ryanodine (30 μM) and caffeine (10 mM) through an open‐lock of Ca2+‐induced Ca2+ release (CICR)‐related channels. The results show that action potentials, discharged repeatedly during the early period of a long membrane depolarization, undergo a progressive change in configuration but can each trigger a constant rise in [Ca2+]i. Intracellular Ca2+ stores have a role, especially in accelerating the falling phase of the action potential‐triggered [Ca2+]i transients by replenishing cytosolic Ca2+. No evidence was provided for the involvement of CICR in the action potential‐triggered [Ca2+]i transient. British Journal of Pharmacology (1997) 122, 477–486; doi:10.1038/sj.bjp.0701407

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British Journal of Pharmacology

Tập 122 Số 3

477-486

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