Search

Biophysical properties of A-type K(+) currents (I(A)) in myenteric neurons from guinea-pig small intestine were studied. I(A) was present in both AH- and S-type myenteric neurons. Reduction of external Ca(2+) did not affect the current. Current density was 13.5+/-10.2 pA/pF in 68 AH-type neurons and 23.4+/-8.2 pA/pF in 31 S-type neurons. S-type neurons appeared to be a homogeneous group based on density of I(A). AH-type neurons were subdivided into two groups with current densities of 9.4+/-4.3 and 25.4+/-4.3 pA/pF. All other biophysical properties of the current were not statistically different for AH- and S-type neurons. Steady-state activation and inactivation curves showed half-activation potentials at -7 mV (k=15. 0 mV) and -86 mV (k=11.5 mV). The curves overlapped at potentials near the resting potential of approximately -55 mV. Time constants for activation ranged from 3.6 to 0.52 ms at test potentials between -20 and 50 mV. Inactivation time constants fell between 41.5 and 11 ms at test potentials between -20 and 50 mV. Time constants for recovery from inactivation fit a double-exponential curve with fast and slow recovery times of 11 and 550 ms. 4-Aminopyridine suppressed I(A) when it was activated at -20 mV following a pre-pulse to -110 mV. Addition of Zn(2+) in the external solution resulted in a concentration-dependent shift of the activation and inactivation curves in the depolarized direction. Zn(2+) slowed the activation and inactivation kinetics of I(A) by factors of 3.3- and 1.2-fold over a wide range of potentials. Elevation of external H(+) suppressed the effect of Zn(2+) with a pK of 7.3-7.4. The effects of Zn(2+) were interpreted as not being due to surface charge screening, because the affinity of Zn(2+) for its binding site on the A-channel was estimated to be between 170 and 312 microM, while the background concentration of Mg(2+) was 10 mM. The enteric nervous system is perceived as an independent integrative nervous system (brain-in-the-gut) that is responsible for local organizational control of motility and secretory patterns of gut behavior. AH- and S-type neurons are synaptically interconnected to form the microcircuits of the enteric nervous system. The results suggest that I(A) is a significant determinant of neuronal excitability for both the firing of nerve impulses and the various synaptic events in the two types of neurons.

Patch-clamp recording was used to study rectifying K+ currents in myenteric neurons in short-term culture. In conditions that suppressed Ca2+ -activated K+ current, three kinds of voltage-activated K+ currents were identified by their voltage range of activation, inactivation, kinetics and pharmacology. These were A-type current, delayed outwardly rectifying current (I(K),dr) and inwardly rectifying current (I(K),ir). I(K),ir consisted of an instantaneous component followed by a time-dependent current that rapidly increased at potentials negative to -80 mV. Time-constant of activation was voltage-dependent with an e-fold decrease for a 31-mV hyperpolarization amounting to a decrease from 800 to 145 ms between -80 and -100 mV. I(K),ir did not inactivate. I(K),ir was abolished in K+ -free solution. Increases in external K+ increased I(K),ir conductance in direct relation to the square root of external K+ concentration. Activation kinetics were accelerated and the activation range shifted to more positive K+ equilibrium potentials. I(K),ir was suppressed by external Cs+ and Ba2+ in a concentration-dependent manner. Ca2+ and Mg+ were less effective than Ba2+. I(K),ir was unaffected by tetraethylammonium ions. I(K),dr was activated at membrane potentials positive to - 30 mV with an e-fold decrease in time-constant of activation from 145 to 16 ms between -20 and 30 mV. It was half-activated at 5 mV and fully activated at 50 mV. Inactivation was indiscernible during 2.5 s test pulses. I(K),dr was suppressed in a concentration-, but not voltage-dependent manner by either tetraethylammonium or 4-aminopyridine and was insensitive to Cs+. The results suggest that I(K),ir may be important in maintaining the high resting membrane potentials found in afterhyperpolarization-type enteric neurons. They also suggest importance of I(K),ir channels in augmentation of the large hyperpolarizing after-potentials in afterhyperpolarization-type neurons and the hyperpolarization associated with inhibitory postsynaptic potentials. I(K),dr in afterhyperpolarization-type enteric neurons has overall kinetics and voltage behaviour like delayed rectifier currents in other excitable cells where the currents can also be distinguished from A-type and Ca2+ -activated K+ current.