Roles of Calcium Ions and Cyclic AMP in Olfactory Transduction

The roles of Ca2 + and cAMP in olfactory transduction were explored using agents which affect calcium channels and second messenger systems. These agents were applied at certain calculated final concentrations onto olfactory epithelia of urethane-anesthetized frogs (Sana PiPlens) by two-sec aerosol spray. During extracellular recording, saturated vapors of isoamyl acetate were delivered every 100 sec in 0.3 sec pulses to produce an electroolfactogram (EOG). Inorganic cations that block inward calcium currents inhibit EOG responses with the following rank order: (La3+) > (Zn2+, Cd2+) > (Al3+, Ca2+, Sr2+) > (Co2+). Application of 7.5 mM La3+ eradicates £0G's, while Ba2+ (which can carry more current that Ca2+) initially produces significant enhancement (F=43.04, p<0.001, df=19). Magnesium ion has no effect on EOG's at 7.5 mM, while 1.5 X 10"4M Ca2+ is significantly inhibitory (F=5.74; p=0.0355; df=12). Control aerosol sprays of distilled water depress EOG's by an average of 5%. The organic calcium channel antagonists diltiazem and verapamil inhibit EOG's by 17% and 36X, respectively, at a concentration of 1.5 X 10~*M. Verapamil produces significant inhibition (F=17.17; p=0.002; df=ll) at 1.5 X 10" 5 M, while the 1,4-dihydropyridine calcium channel antagonists, nicardipine and nifedipine, do not inhibit beyond 1% DMSO controls. Several calmodulin antagonists decrease EOG's, but without correlation to their anti-calmodulin potency. Application of 1.5 X 10"*M chlorpromazine and N-(6-aminohexyl)-5-chloro-l-naphthalenesulfonamide inhibit EOG's by 31% and 27%, respectively, while trifluoperazine inhibits by 23%. Dibutyryl cAMP, a lipophilic mimic of cAMP, produces 54% inhibition at 1.5 X 10" *M. Dibutyryl cGMP, cGMP, cAMP, and adenosine all decrease EOG's by less than 15% compared to distilled water controls. Forskolin, a reversible activator of adenylate cyclase, inhibits EOG's by 57% at 1.5 X 10"5M, which is significant beyond the 1% DMSO controls (F=17.17; p=0.002; df=ll). These data support the hypothesis that Ca2+ participates in olfactory transduction. Calcium ions could serve as charge carriers, second messengers, or both. Cyclic AMP could be involved with the primary excitatory process or sensory adaptation, or both

Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys-5

<p><b>Copyright information:</b></p><p>Taken from "Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys"</p><p>BMC Neuroscience 2006;7():5-5.</p><p>Published online 12 Jan 2006</p><p>PMCID:PMC1369004.</p><p>Copyright © 2006 Winegar and MacIver; licensee BioMed Central Ltd.</p> the larger EPSP. , () The FV was isolated with CNQX (8.6 μM) and APV (125 μM) to block AMPA/kainate and NMDA receptors, respectively. , Partial block of a FV by 60 nM TTX (green trace). , Isoflurane produced small reductions of FV amplitudes (blue traces). , Concentration dependence of the depression of FV amplitudes by isoflurane. Data were normalized to control conditions in the absence of drug. Each point represents the mean of multiple experiments carried out in different slice preparations (n = 6 each data point), with standard deviations represented by the error bars. The dashed line is a least-squares fit to a Boltzmann relation with an EC= ~12 vol % and a Hill coefficient of 2 (χ= 2.5). All measurements were made following at least a 20 minute period for the perfusion system to equilibrate

Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys-2

<p><b>Copyright information:</b></p><p>Taken from "Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys"</p><p>BMC Neuroscience 2006;7():5-5.</p><p>Published online 12 Jan 2006</p><p>PMCID:PMC1369004.</p><p>Copyright © 2006 Winegar and MacIver; licensee BioMed Central Ltd.</p>SP depression under each condition were almost identical. The actions of these treatments are shown for EPSP depression (), FV-EPSP curve slopes (I/O slopes; ) and paired-pulse facilitation (PPF; ). Each bar represents the mean ± standard deviation for at least five experiments from different slice preparations. Note that each treatment substantially depressed EPSPs but only isoflurane and low Caproduced a significant change in the I/O slope compared to TTX (p < 0.001 in both cases, ANOVA). PPF with isoflurane and low Cawas also significantly greater than with TTX (p < 0.001 and p < 0.001 respectively, ANOVA)

Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys-4

<p><b>Copyright information:</b></p><p>Taken from "Isoflurane depresses hippocampal CA1 glutamate nerve terminals without inhibiting fiber volleys"</p><p>BMC Neuroscience 2006;7():5-5.</p><p>Published online 12 Jan 2006</p><p>PMCID:PMC1369004.</p><p>Copyright © 2006 Winegar and MacIver; licensee BioMed Central Ltd.</p>epresentative whole-cell perforated patch in the pyramidal cell body layer of the hippocampal CA1 region. 100 ms voltage pulses to -30 mV were applied at 10 s intervals to elicit spikes (V= -70 mV). Currents in green show four spikes recorded after a 15 min exposure to 60 nM TTX. At right are overlays of spike currents recorded before and after a 10 min exposure to 350 μM isoflurane (1 MAC). The blue traces were recorded after exposure to isoflurane