The ionic mechanisms underlying excitability in neurons of parasympathetic ganglia of the heart and the actions of neurotransmitters on their function will be studied. Neurotransmitters influence the function of a variety of ion channels and intracellular proteins in excitable cells to alter resting and active electrical properties and, hence, the physiological responses of the cell. Ionic currents will be studied in neurons of both in situ guinea-pig cardiac ganglia and dissociated ganglion cells from the atria of guinea-pigs grown in tissue culture using single channel and whole cell patch clamp recording techniques. The primary objective is to characterize the biophysical and pharmacological properties of potassium-selective ion channels in cardiac neurons and the possible modulation of potassium channels by various neurotransmitters. Experiments will focus on specific ion conductance mechanisms underlying the slow (potassium-selective) synaptic response mediated by muscarinic receptors (m-AChR) and to determine the pharmacological sensitivity of the m-AChR potassium channels to specific muscarinic agonists and antagonists. The effect of neurotransmitters (and specific antagonists) on the kinetic and permeability properties of identified potassium channels will be determined from measurements of ionic currents through individual potassium channels. The patch clamp method offers unique advantages for the study of membrane responses that involve intracellular mediators (biochemical second messengers) between receptor and ion channel, because of the ability to control the ion composition and locus of drug application on both intracellular and extracellular surfaces of the cell membrane. This novel study will contribute to understanding neurotransmitter modulation of ion channels in cardiac ganglion cells and elucidate mechanisms by which a diversity of chemical signalling can act to influence neural regulation of the heart.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035422-04
Application #
3349283
Study Section
Cardiovascular Study Section (CVA)
Project Start
1985-12-01
Project End
1990-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Miami School of Medicine
Department
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33101
Adams, D J; Trequattrini, C (1998) Opioid receptor-mediated inhibition of omega-conotoxin GVIA-sensitive calcium channel currents in rat intracardiac neurons. J Neurophysiol 79:753-62
Cuevas, J; Harper, A A; Trequattrini, C et al. (1997) Passive and active membrane properties of isolated rat intracardiac neurons: regulation by H- and M-currents. J Neurophysiol 78:1890-902
Cuevas, J; Adams, D J (1997) M4 muscarinic receptor activation modulates calcium channel currents in rat intracardiac neurons. J Neurophysiol 78:1903-12
Poth, K; Nutter, T J; Cuevas, J et al. (1997) Heterogeneity of nicotinic receptor class and subunit mRNA expression among individual parasympathetic neurons from rat intracardiac ganglia. J Neurosci 17:586-96
Cuevas, J; Adams, D J (1996) Vasoactive intestinal polypeptide modulation of nicotinic ACh receptor channels in rat intracardiac neurones. J Physiol 493 ( Pt 2):503-15
Nutter, T J; Adams, D J (1995) Monovalent and divalent cation permeability and block of neuronal nicotinic receptor channels in rat parasympathetic ganglia. J Gen Physiol 105:701-23
Rusko, J; Van Slooten, G; Adams, D J (1995) Caffeine-evoked, calcium-sensitive membrane currents in rabbit aortic endothelial cells. Br J Pharmacol 115:133-41
Katnik, C; Adams, D J (1995) An ATP-sensitive potassium conductance in rabbit arterial endothelial cells. J Physiol 485 ( Pt 3):595-606
Cuevas, J; Adams, D J (1994) Local anaesthetic blockade of neuronal nicotinic ACh receptor-channels in rat parasympathetic ganglion cells. Br J Pharmacol 111:663-72
Xu, Z J; Adams, D J (1993) Alpha-adrenergic modulation of ionic currents in cultured parasympathetic neurons from rat intracardiac ganglia. J Neurophysiol 69:1060-70

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