Raising the ambient potassium ion concentration enhances carbachol stimulated phosphoinositide hydrolysis in rat brain hippocampal and cerebral cortical miniprisms

Publisher Website
Google Scholar
Abstract
The influence of the ambient potassium ion concentration ([K+]_ upon agonist stimulated hydrolysis of phosphoinositides (PI) has been studied in isolated miniprisms of rat hippocampus and cerebral cortex. When the external [K+] was raised from 6 to 18 mmol/l, there was little or no increase in the hydrolysis of PI in the absence of agonist, however, carbachol (100 μmol/l) stimulated hydrolysis was greatly enhanced in both brain regions studied. Thus, carbachol stimulated the hydrolysis of PI to 146% and 386% of control levels at potassium concentrations of 5.8 and 18.2 mmol/l, respectively, in the rat hippocampus. A similar enhancement of muscarine (100 μmol/l) stimulation was observed in cortical miniprisms with 18 mmol/l [K+]. A further enhancement was seen at higher ambient [K+], although basal hydrolysis of PI was then also increased. The carbachol-stimulated hydrolysis of PI found at both 6 and raised [K+] was prevented by atropine (1 and 10 μmol/l) and tetraethylammonium (20 mmol/l), but not by 10 mmol/l Mg2+. Pirenzepine (50 nmol/l) also reduced this response. The ions Cs+ and Rb+ (but not Li+ or Tris+) produced a similar enhancement of the carbachol stimulation to that found with K+. At a buffer [K+] of 6 mmol/l, noradrenaline (100 μmol/l) produced a 2-fold increase in the hydrolysis of PI whereas 5-hydroxytryptamine (100 μmol/l) and histamine (500 μmol/l) had little or no effect. However, histamine and 5-hydroxytryptamine did stimulate the hydrolysis of PI when [K+] was increased. Miniprism ATP content was not changed by a rise in [K+] to 18 mmol/l. The significance of these results is discussed in terms of the postsynaptic cellular events following cholinergic stimulation.