IONIC BASIS OF EXCITABILITY IN INTRINSIC CARDIAC NEURONS

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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.