Presynaptic action of adenosine on a 4-aminopyridine-sensitive current in the rat carotid body.
1. Plasma adenosine concentration increases during hypoxia to a level that excites carotid body chemoreceptors by an undetermined mechanism. We have examined this further by determining the electrophysiological responses to exogenous adenosine of sinus nerve chemoafferents in vitro and of whole-cell currents in isolated type I cells. 2. Steady-state, single-fibre chemoafferent discharge was increased approximately 5-fold above basal levels by 100 microM adenosine. This adenosine-stimulated discharge was reversibly and increasingly reduced by methoxyverapamil (D600, 100 microM), by application of nickel chloride (Ni2+, 2 mM) and by removal of extracellular Ca2+. These effects strongly suggest a presynaptic, excitatory action of adenosine on type I cells of the carotid body. 3. Adenosine decreased whole-cell outward currents at membrane potentials above -40 mV in isolated type I cells recorded during superfusion with bicarbonate-buffered saline solution at 34-36 C. This effect was reversible and concentration dependent with a maximal effect at 10 microM. 4. The degree of current inhibition induced by 10 microM adenosine was voltage independent (45.39 +/- 2. 55 % (mean +/- s.e.m.) between -40 and +30 mV) and largely ( approximately 75 %), but not entirely, Ca2+ independent. 4-Aminopyridine (4-AP, 5 mM) decreased the amplitude of the control outward current by 80.60 +/- 3.67 % and abolished the effect of adenosine. 5. Adenosine was without effect upon currents near the resting membrane potential of approximately -55 mV and did not induce depolarization in current-clamp experiments. 6. We conclude that adenosine acts to inhibit a 4-AP-sensitive current in isolated type I cells of the rat carotid body and suggest that this mechanism contributes to the chemoexcitatory effect of adenosine in the whole carotid body.
Department of Physiology, The Medical School, University of Birmingham, Birmingham B15 2TT, UK.
C
C
Vandier
A F
AF
Conway
R C
RC
Landauer
P
P
Kumar
D015761:4-Aminopyridine / Q000494:pharmacology*; D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D015761:4-Aminopyridine; D000241:Adenosine; D002118:Calcium