Prepulse-induced mode 2 gating behavior with and without β-adrenergic stimulation in cardiac L-type Ca channels

Yuji Hirano, Takashi Yoshinaga, Mitsushige Murata, Masayasu Hiraoka

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Mode 2 gating of L-type Ca channels is characterized by high channel open probability (NP(o)) and long openings. In cardiac myocytes, this mode is evoked physiologically in two apparently different circumstances: membrane depolarization (prepulse facilitation) and activation of protein kinase A. To examine whether the phosphorylation mechanism is involved during prepulse- induced facilitation of cardiac L-type Ca channels, we used isolated guinea pig ventricular myocytes to analyze depolarization-induced modal gating behavior under different basal levels of phosphorylation. In control, NP(o) measured at 0 mV was augmented as the duration of prepulse to + 100 mV was prolonged from 50 to 400 ms. This was due to the induction of mode 2 gating behavior clustered at the beginning of test pulses. Analysis of open time distribution revealed that the prepulse evoked an extra component, the time constant of which is not dependent on prepulse duration. When isoproterenol (1 μM) was applied to keep Ca channels at an enhanced level of phosphorylation, basal NP(o) without prepulse was increased by a factor of 3.6 ± 2.2 (n = 6). Under these conditions, prepulse further increased NP(o) by promoting long openings with the same mode 2 kinetics of transition to gating (τ ~ 200 ms at + 100 mV). Likewise, recovery from mode 2 gating, as estimated by the decay of averaged unitary current, was not affected after β-stimulation (τ ~ 25 ms at 0 mV). The kinetic behavior independent from the basal level of phosphorylation or activity of cAMP-dependent protein kinase suggests that prepulse facilitation of the cardiac Ca channel involves a mechanism directly related to voltage-dependent conformational change rather than voltage-dependent phosphorylation.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume276
Issue number6 45-6
Publication statusPublished - 1999
Externally publishedYes

Fingerprint

Phosphorylation
Adrenergic Agents
Depolarization
Cyclic AMP-Dependent Protein Kinases
Kinetics
Electric potential
Isoproterenol
Cardiac Myocytes
Muscle Cells
Guinea Pigs
Chemical activation
Membranes
Recovery
Prepulse Inhibition

Keywords

  • Isoproterenol
  • Phosphorylation
  • Prepulse facilitation

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Prepulse-induced mode 2 gating behavior with and without β-adrenergic stimulation in cardiac L-type Ca channels. / Hirano, Yuji; Yoshinaga, Takashi; Murata, Mitsushige; Hiraoka, Masayasu.

In: American Journal of Physiology - Cell Physiology, Vol. 276, No. 6 45-6, 1999.

Research output: Contribution to journalArticle

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