P. Sah, DIFFERENT CALCIUM CHANNELS ARE COUPLED TO POTASSIUM CHANNELS WITH DISTINCT PHYSIOLOGICAL ROLES IN VAGAL NEURONS, Proceedings - Royal Society. Biological Sciences, 260(1357), 1995, pp. 105-111
Whole-cell and sharp microelectrode recordings were obtained from neur
ons of rat dorsal motor nucleus of the vagus (DMV) in transverse slice
s of the rat medulla maintained in vitro. Calcium currents were studie
d with sodium currents blocked with tetrodotoxin, potassium currents b
locked by perfusing the cell with caesium as the main cation and using
barium as the charge carrier. From a holding potential of -60 mV, inw
ard currents activated at potentials positive of -50 mV and peaked aro
und 0 mV. Voltage clamping the neuron at more hyperpolarised potential
s did not reveal any low-threshold inward current. The inward current
was effectively blocked by cadmium (100 mu M) and nicked (1 mM), sugge
sting that it is carried by voltage-dependent calcium channels. The in
ward current could be separated into three pharmacologically distinct
components: 40% of the whole cell current was omega-conotoxin sensitiv
e; 20% of the current was nifedipine sensitive; and the rest was block
ed by high concentrations of cadmium and nickel. This remaining curren
t cannot be due to P-type calcium channels as omega-agatoxin had no ef
fect on the inward current. Nifedipine had no significant effect on th
e action potential. Application of omega-conotoxin reduced the calcium
component of the action potential and significantly reduced the potas
sium current underlying the afterhyperpolarization. Application of cha
rybdotoxin slowed action potential repolarization. When N-type calcium
channels were blocked with omega-conotoxin, charybdotoxin was still e
ffective in slowing repolarization. In contrast, charybdotoxin was ine
ffective when calcium influx was blocked with the nonspecific calcium
channel blocker cadmium. These results show that, during the action po
tential, both omega-conotoxin-sensitive and omega-conotoxin-insensitiv
e calcium channels contribute to calcium influx. Calcium influx via N-
type channels is responsible for activating potassium channels underly
ing the afterhyperpolarization. In contrast, influx via omega-CgTx and
nifedipine-insensitive channels is responsible for activating potassi
um channels contributing to action potential repolarization. Calcium-a
ctivated potassium channels are thought to be in close proximity to vo
ltage-dependent calcium channels. These results therefore suggest that
in vagal neurons different calcium channels are colocalized with diff
erent calcium-activated potassium channels that subserve distinct func
tional roles.