Molecular aspects of adrenergic modulation of cardiac L-type Ca2+ channels

Cardiovasc Res. 2005 Jan 1;65(1):28-39. doi: 10.1016/j.cardiores.2004.09.028.

Abstract

L-type Ca(2+) channels are predominantly regulated by beta-adrenergic stimulation, enhancing L-type Ca(2+) current by increasing the mean channel open time and/or the opening probability of functional Ca(2+) channels. Stimulation of beta-adrenergic receptors (ARs) results in an increased cyclic adenosine monophosphate (cAMP) production by adenylate cyclase (AC) and consequently activation of protein kinase (PK) A and phosphorylation of L-type Ca(2+) channels by this enzyme. Beta(1)-Adrenergic receptors couple exclusively to the G protein Gs, producing a widespread increase in cAMP levels in the cell, whereas beta(2)-adrenergic receptors couple to both Gs and Gi, producing a more localized activation of L-type Ca(2+) channels. Other signaling intermediates (protein kinase C, protein kinase G or protein tyrosine kinase (PTK)) either have negative effects on L-type Ca(2+) current, or they interact with the stimulatory effect of the protein kinase A pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic Agents / pharmacology*
  • Amino Acid Sequence
  • Animals
  • Calcium / metabolism
  • Calcium Channels, L-Type / drug effects
  • Calcium Channels, L-Type / genetics
  • Calcium Channels, L-Type / metabolism*
  • Humans
  • Ion Channel Gating*
  • Molecular Sequence Data
  • Myocardium / metabolism*
  • Protein Kinases / metabolism
  • Receptors, Adrenergic / metabolism*
  • Sequence Alignment

Substances

  • Adrenergic Agents
  • Calcium Channels, L-Type
  • Receptors, Adrenergic
  • Protein Kinases
  • Calcium